The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer.

In triple-negative breast cancer (TNBC), stromal restriction of CD8+ T cells associates with poor clinical outcomes and lack of responsiveness to immune-checkpoint blockade (ICB). To identify mediators of T cell stromal restriction, we profiled murine breast tumors lacking the transcription factor Stat3, which is commonly hyperactive in breast cancers and promotes an immunosuppressive tumor microenvironment. Expression of the cytokine Chi3l1 was decreased in Stat3-/- tumors. CHI3L1 expression was elevated in human TNBCs and other solid tumors exhibiting T cell stromal restriction. Chi3l1 ablation in the polyoma virus middle T (PyMT) breast cancer model generated an anti-tumor immune response and delayed mammary tumor onset. These effects were associated with increased T cell tumor infiltration and improved response to ICB. Mechanistically, Chi3l1 promoted neutrophil recruitment and neutrophil extracellular trap formation, which blocked T cell infiltration. Our findings provide insight into the mechanism underlying stromal restriction of CD8+ T cells and suggest that targeting Chi3l1 may promote anti-tumor immunity in various tumor types.

Concepts, electrode configuration, characterization, and data analytics of electric and electrochemical microfluidic platforms: a review.

Microfluidic cytometry (MC) and electrical impedance spectroscopy (EIS) are two important techniques in biomedical engineering. Microfluidic cytometry has been utilized in various fields such as stem cell differentiation and cancer metastasis studies, and provides a simple, label-free, real-time method for characterizing and monitoring cellular fates. The impedance microdevice, including impedance flow cytometry (IFC) and electrical impedance spectroscopy (EIS), is integrated into MC systems. IFC measures the impedance of individual cells as they flow through a microfluidic device, while EIS measures impedance changes during binding events on electrode regions. There have been significant efforts to improve and optimize these devices for both basic research and clinical applications, based on the concepts, electrode configurations, and cell fates. This review outlines the theoretical concepts, electrode engineering, and data analytics of these devices, and highlights future directions for development.

A dual-task approach to inform the taxonomy of inhibition-related processes.

Response inhibition is key to controlled behavior and is commonly investigated with the stop-signal paradigm. The authors investigated how response inhibition is situated within a taxonomy of control processes by combining multiple forms of control within dual tasks. Response inhibition, as measured by stop-signal reaction time (SSRT), was impaired when combined with shape matching, but not the flanker task, and when combined with cued task switching, but not predictable task switching, suggesting that response inhibition may be weakly or variably impaired when combined with selective attention and set shifting demands, respectively. Response inhibition was also consistently impaired when combined with the N-back or directed forgetting tasks, putative measures of working memory. Impairments of response inhibition by other control demands appeared to be primarily driven by task context, as SSRT slowing was similar for trials where control demands were either high (e.g., task switch) or low (e.g., task stay). These results demonstrate that response inhibition processes are often impaired in the context of other control demands, even on trials where direct engagement of those other control processes is not required. This suggests a taxonomy of control in which response inhibition overlaps with related control processes, especially working memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.

p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110αHR) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110αHR bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110αHR mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.

Exploiting Mouse Models to Recapitulate Clinical Tumor Dormancy and Recurrence in Breast Cancer.

Breast cancer recurrence and metastasis from activated dormant tumors remain the leading causes in disease morbidity. Women with estrogen receptor-positive breast cancer that accounts for nearly 80% of all cases face a lifelong risk of relapse after initial treatment. The biology of dormant tumors and dormant cancer cells that give rise to recurrent disease and metastasis remain to be understood for us to overcome the clinical challenges that they bring. The selection and optimization of preclinical models to recapitulate dormancy and recurrence in patients is critical for studying the underlying cellular and environmental factors. Here, we provide a brief review of studies that utilize mouse models to dissect the mechanisms of dormancy and therapeutic strategies to avert recurrence. This review specifically accentuates the versatility and benefits of immunocompetent transgenic mouse models that can be manipulated to recapitulate primary dormancy, metastatic dormancy, and post-therapy dormancy.

Trends in colorectal cancer incidence in Ho Chi Minh City, Vietnam (1996-2015): Joinpoint regression and age-period-cohort analyses.

BACKGROUND: Little is known about the trends in colorectal cancer (CRC) in Vietnam. We aimed to investigate the trends in epidemiology and anatomical subsites of CRC in Ho Chi Minh City, Vietnam. METHODS: Based on the Ho Chi Minh City Cancer Registry data during 1996-2015, we calculated the average annual percent changes (AAPCs) of the age-standardized incidence rates (ASRs) by sex, age groups, and anatomical subsites, using joinpoint regressions analysis. We further performed age-period-cohort (APC) analysis using the United States National Cancer Institute's web-based statistical tool to explore the underlying reason for the incidence trend. RESULTS: Over 20 years the overall ASR of CRC increased from 10.5 to 17.9 per 100,000, a 1.7-fold increase. CRC incidence elevated more rapidly in men (AAPC 4.7, 95%CI 2.2-7.3) than in women (AAPC 2.6, 95%CI 0.6-4.8). The highest and lowest increasing rates of ASRs were observed in the 50-64-year-old age group (AAPC 5.3, 95%CI 2.8-7.9) and < 50-year-old age group (AAPC 1.1, 95%CI -0.7 to 2.9), respectively. Regarding subsites, rectal cancer had the highest rate of increase (AAPC 3.3, 95%CI 1.0-5.7). Furthermore, the APC analysis indicated significant increases in CRC incidence in birth cohorts after 1975 in both genders. CONCLUSIONS: The CRC incidence in Ho Chi Minh City increased, with the more prominent rates being among men and older populations, in rectal subsites, and in people born after 1975. The upward trend of CRC incidence in Ho Chi Minh City may be due to the adoption of a westernized lifestyle.

Emergence of ß1 integrin-deficient breast tumours from dormancy involves both inactivation of p53 and generation of a permissive tumour microenvironment.

The molecular and cellular mechanisms underlying mammary tumour dormancy and cancer recurrence are unclear and remain to be elucidated. Here, we report that mammary epithelial-specific disruption of ß1 integrin in a murine model of Luminal B human breast cancer drastically impairs tumour growth with proliferation block, apoptosis induction and cellular senescence. ß1 integrin-deficient dormant lesions show activation of the tumour suppressor p53, and tumours that circumvent dormancy possess p53 mutation analogous to those in human disease. We further demonstrate that mammary epithelial deletion of p53 in ß1 integrin-deficient mice fully rescues tumour dormancy and bypasses cellular senescence. Additionally, recurrent ß1 integrin-deficient tumours exhibit fibrosis with increased cancer-associated fibroblast infiltration and extracellular matrix deposition, absent in fast-growing ß1 integrin/p53-deficient lesions. Taken together, these observations argue that ß1 integrin modulates p53-dependent cellular senescence resulting in tumour dormancy and that pro-tumourigenic stromal cues and intrinsic genetic mutation are required for dormancy exit.

Immunomagnetic separation in a novel cavity-added serpentine microchannel structure for the selective isolation of lung adenocarcinoma cells.

The manipulation and separation of circulating tumor cells (CTCs) in continuous fluidic flows play an essential role in various biomedical applications, particularly the early diagnosis and treatment of diseases. Recent advances in magnetic bead development have provided promising solutions to the challenges encountered in CTC manipulation and isolation. In this study, we proposed a biomicrofluidic platform for specifically isolating human lung carcinoma A549 cells in microfluidic channels. The principle of separation was based on the effect of the magnetic field on aptamer-conjugated magnetic beads, also known as immunomagnetic beads, in a serpentine microchannel with added cavities (SMAC). The magnetic cell separation performance of the proposed structure was modeled and simulated by using COMSOL Multiphysics. The experimental procedures for aptamer molecular conjugation on 1.36 µm-diameter magnetic beads and magnetic bead immobilization on A549 cells were also reported. The lung carcinoma cell-bead complexes were then experimentally separated by an external magnetic field. Separation performance was also confirmed by optical microscopic observations and fluorescence analysis, which showed the high selectivity and efficiency of the proposed system in the isolation and capture of A549 cells in our proposed SMAC. At the flow rate of 5 µL/s, the capture rate of human lung carcinoma cells exceeded 70% in less than 15 min, whereas that of the nontarget cells was approximately 4%. The proposed platform demonstrated its potential for high selectivity, portability, and facile operation, which are suitable considerations for developing point-of-care applications for various biological and clinical purposes.

Factors Associated With the Intention to Participate in Coronavirus Disease 2019 Frontline Prevention Activities Among Nursing Students in Vietnam: An Application of the Theory of Planned Behavior.

Introduction: Medical students have been serving as a key part of the frontline health workforce responding to the coronavirus disease 2019 (COVID-19) pandemic globally. Their contribution is especially important in the resource-scarce settings of developing nations such as Vietnam. Yet, the intention of medical students, in particular, nursing students, to participate in COVID-19 frontline prevention activities has not been well-understood. This study aimed to examine factors associated with the intentionto participate in COVID-19 frontline prevention activities among Vietnamese nursing students. Methods: A cross-sectional study was conducted on a total of 597 students in December 2020 in Hanoi, Vietnam. Information regarding the socioeconomic characteristics of participants, their source of COVID-19 related knowledge, and their perception and attitude toward participating in COVID-19 frontline activities [based on Theory of Planned Behavior (TPB)] was collected. A hierarchical regression model was employed to examine the association between intentions of students and associated factors. Results: A positive intention to participate in COVID-19 frontline prevention activities was found (mean score of 25.3 over 35; SD = 4.4; min = 5; max = 35). Attitude toward behavior, subjective norms, and perceived behavioral control (PBC) was found to be significantly associated with the intention of students. These variables explained the 37% variation in the intention of students in the model. Among three factors, subjective norm showed the strongest correlation with intention of students (ß = 0.358; p < 0.001). Obtaining information from official sources and community was also found to be positively correlated with intention to participate. Conclusion: Most of the respondents reported a positive intention to participate in COVID-19 frontline prevention activities. The findings suggested that the TPB was a good instrument to predict the intention to perform behavior among Vietnamese students. Enhancing the positive attitude of students, encouraging family and community supports, and providing adequately essential resources will contribute to optimizing the participation of students to confront COVID-19.

In-air particle generation by on-chip electrohydrodynamics.

Electrohydrodynamic atomization has been emerging as a powerful approach for respiratory treatment, including the generation and delivery of micro/nanoparticles as carriers for drugs and antigens. In this work, we present a new conceptual design in which two nozzles facilitate dual electrospray coexisting with ionic wind at chamfered tips by a direct current power source. Experimental results by a prototype have demonstrated the capability of simultaneously generating-and-delivering a stream of charged reduced particles. The concept can be beneficial to pulmonary nano-medicine delivery since the mist of nanoparticles is migrated without any restriction of either the collector or the assistance of external flow, but is pretty simple in designing and manufacturing devices.

Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996-2015): a population-based study.

BACKGROUND: The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. METHODS: A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996-2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. RESULTS: In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996-2000 (95% confidence interval [95% CI]: 2.2-2.6) to 7.5 per 100,000 during 2011-2015 (95% CI: 7.3-7.9), corresponded to an overall APC of 8.7 (95% CI 7.6-9.9). The APC in men and women was 6.2 (95% CI: 4.2-8.2) and 9.2 (95% CI: 8.0-10.4), respectively. The incidence rate in the < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3-12.0)). CONCLUSIONS: There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.

Financial development and energy poverty: global evidence.

This study aims to shed light on the determinants of energy poverty by examining the role of financial development. Notably, the study analyses the multidimensional effects of financial development (including two subsectors and three dimensions on five indicators of energy poverty). Various estimates are applied with a global sample of 65 economies, consisting of 36 low- and lower-middle-income economies and 29 upper-middle-income economies for 2002-2015. First, financial development can alleviate energy poverty. Second, the results are properly consistent across the two subsectors and three dimensions. Third, the two subsectors and three dimensions of financial development are found to reduce energy poverty in low- and lower-middle-income economies but have heteroscedastic effects in upper-middle-income economies.

Trends in breast cancer incidence in Ho Chi Minh City 1996-2015: A registry-based study.

The burden of breast cancer in Vietnam has not been documented. This study sought to estimate the incidence of breast cancer in Ho Chi Minh City, the largest economic center of Vietnam, from 1996 to 2015. This was a population-based study using the Ho Chi Minh City Cancer Registry as a source of data (coverage period: 1996-2015). The Registry adopted the International Classification of Diseases for Oncology, 3rd Edition for the classification of primary sites and morphology, and guidelines from the International Agency for Research on Cancer and the International Association of Cancer Registries. Using the population statistics from census data of Ho Chi Minh City, the point incidence of breast cancer for 5-year period was estimated. Based on the national population, we calculated the age-standardized rate (ASR) of breast cancer between 1996 and 2015. Overall 14,222 new cases of breast cancer (13,948 women, or 98%) had been registered during the 1996-2015 period; among whom, just over half (52%) were in the 2nd stage and 26% in the 3rd and 4th stages. In women, the median age at diagnosis was 50 years and there was a slight increase over time. The ASR of breast cancer during the 2011-2015 period was 107.4 cases per 100,000 women, representing an increase of 70% compared to the rate during the 1996-2000 period. In men, there was also a significant increase in the ASR: from 1.13 during the 1996-2001 period to 2.32 per 100,000 men during the 2011-2015 period. These very first data from Vietnam suggest that although the incidence of breast cancer in Vietnam remains relatively low, it has increased over time.

A Cross-Sectional Study about Knowledge, Awareness and Perception of Risk Factors for Cancer among Cancer-Patients Relatives and Healthy Adults in Ho Chi Minh City, Vietnam.

BACKGROUND AND AIMS: Although cancer is common in Ho Chi Minh city, Vietnam, the community awareness is still unknown. The primary objective of this study was to examine and compare the knowledge and risk perceptions of cancer possessed by cancer patients - relatives and healthy adults in Ho Chi Minh City, Vietnam. METHODS: A cross-sectional study was conducted from June to August 2019. Cancer patients and their relatives were drawn from those who were hospitalized in the Oncology Hospital, Ho Chi Minh City. Healthy individuals were those without a known diagnosis of cancer, and they were drawn from the participants of the Vietnam Osteoporosis Study. A total of 533 participants including 249 patients and relatives (cancerous group) and 284 healthy individuals (healthy group), were asked to respond to a structured questionnaire that was comprised of items concerning cancer knowledge, risk factor perception, and general attitude towards cancer, using Yes, No, or Likert Scale for response. RESULTS: The findings showed that patients hold poorer knowledge of pathology, signs, symptoms, prevention, and treatment and lower awareness of risk factors but more positive attitude towards cancer as compared to their healthy counterparts. Overall, both groups varied in their cancer knowledge, with many areas remain to be improved. CONCLUSIONS: Knowledge about cancer and its risk factors should be improved among the general population as well as among those with direct experiences with cancer.  Practical implications: The findings provided by this study has major implications for the design of an educational program for cancer patients in clinical settings and awareness programs for the general public as a primary preventive measure for mitigating the cancer burden. Future studies with larger and more diverse samples or qualitative studies exploring the personal narratives of people living with cancer could take advantage from the preliminary data provided by this study. 
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Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo.

Breast cancer is associated with the second highest cancer-associated deaths worldwide. Therefore, understanding the key events that determine breast cancer progression, modulation of the tumor-microenvironment and metastasis, which is the main cause of cancer-associated death, are of great importance. The mammary specific polyomavirus middle T antigen overexpression mouse model (MMTV-PyMT), first published in 1992, is the most commonly used genetically engineered mouse model (GEMM) for cancer research. Mammary lesions arising in MMTV-PyMT mice follow similar molecular and histological progression as human breast tumors, making it an invaluable tool for cancer researchers and instrumental in understanding tumor biology. In this review, we will highlight key studies that demonstrate the utility of PyMT derived GEMMs in understanding the molecular basis of breast cancer progression, metastasis and highlight its use as a pre-clinical tool for therapeutic discovery.

Biological Living Cell in-Flow Detection Based on Microfluidic Chip and Compact Signal Processing Circuit.

Detection and counting of biological living cells in continuous fluidic flows play an essential role in many applications for early diagnosis and treatment of diseases. In this regard, this study highlighted the proposal of a biochip system for detecting and enumerating human lung carcinoma cell flow in the microfluidic channel. The principle of detection was based on the change of impedance between sensing electrodes integrated in the fluidic channel, due to the presence of a biological cell in the sensing region. A compact electronic module was built to sense the unbalanced impedance between the sensing microelectrodes. It consisted of an instrumentation amplifier stage to obtain the difference between the acquired signals, and a lock-in amplifier stage to demodulate the signals at the stimulating frequency as well as to reject noise at other frequencies. The performance of the proposed system was validated through experiments of A549 cells detection as they passed over the microfluidic channel. The experimental results indicated the occurrence of large spikes (up to approximately 180 mV) over the background signal according to the passage of a single A549 cell in the continuous flow. The proposed device is simple-to-operate, inexpensive, portable, and exhibits high sensitivity, which are suitable considerations for developing point-of-care applications.

Non-invasive stereotactic ablative boost in patients with locally advanced cervical cancer.

INTRODUCTION: The current literature is insufficient to guide care for patients with cervical cancer ineligible for brachytherapy. Stereotactic ablative radiotherapy boost is a clinical necessity for these patients, but highly debated among radiation oncologists. OBJECTIVE: To report toxicity and survival outcomes in a large cohort of patients with locally advanced cervical cancer treated with a non-invasive stereotactic ablative radiotherapy boost instead of brachytherapy METHODS: Patients with locally advanced cervical cancer were entered, between January 2008 and December 2018, who were recommended definitive intent external boost after pelvic radiotherapy to 45-50.4 Gy concurrent with weekly cisplatin and simultaneous/sequential nodal boost up to 55-66 Gy. Simulation CT was facilitated using radio-opaque fiducials, empty rectum, dedicated bladder filling, and whole body vaculoplastic immobilization. Kaplan-Meier survival estimates were used to report local/regional recurrences, distant metastases, cancer-specific survival, and overall survival. RESULTS: A total of 25 patients were analyzed. Median follow-up was 25 months (range 6-54). Patients received stereotactic ablative radiotherapy due to refusal of brachytherapy (9/25, 36%), medical co-morbidities limiting implantation (9/25, 36%), or technical infeasibility (7/25, 28%). Typical fractionation was 24-30 Gy in 4-5 fractions (24/25, 96%). The most common long-term toxicity was grade 1-2 vaginal dryness, discomfort, stenosis, and/or dyspareunia (4/25, 16%). One patient had new post-treatment grade 4 fistula in an area of previous tumor erosion (1/25, 4%). Overall survival, cancer specific survival, loco-regional control, and distant control were 95.5%, 100%, 95.5%, and 89.1%, respectively, at 2 years. CONCLUSION: Further study of stereotactic ablative radiotherapy boost for cervical cancer is needed; a brachytherapy-similar approach portends clinical success with 95.5% overall survival and loco-regional control at 2 years.

Functional Redundancy between ß1 and ß3 Integrin in Activating the IR/Akt/mTORC1 Signaling Axis to Promote ErbB2-Driven Breast Cancer.

Integrin receptors coordinate cell adhesion to the extracellular matrix (ECM) to facilitate many cellular processes during malignant transformation. Despite their pro-tumorigenic roles, therapies targeting integrins remain limited. Here, we provide genetic evidence supporting a functional redundancy between ß1 and ß3 integrin during breast cancer progression. Although ablation of ß1 or ß3 integrin alone has limited effects on ErbB2-driven mammary tumorigenesis, deletion of both receptors resulted in a significant delay in tumor onset with a corresponding impairment in lung metastasis. Mechanistically, stiff ECM cooperates with integrin receptors to recruit insulin receptors (IRs) to focal adhesion through the formation of integrin/IR complexes, thereby preventing their lysosomal degradation. ß1/ß3 integrin-deficient tumors that eventually emerged exhibit impaired Akt/mTORC1 activity. Murine and human breast cancers exhibiting enhanced integrin-dependent activity also display elevated IR/Akt/mTORC1 signaling activity. Together, these observations argue that integrin/IR crosstalk transduces mechanical cues from the tumor microenvironment to promote ErbB2-dependent breast cancer progression.

Projecting Cancer Incidence for 2025 in the 2 Largest Populated Cities in Vietnam.

The population size and projected demographics of Vietnam's 2 largest cities, Ho Chi Minh City (HCMC) and Hanoi, will change dramatically over the next decade. Demographic changes in an aging population coupled with income growth and changes in lifestyle will result in a very different distribution of common cancers in the future. The study aimed to project the number of cancer incidence in the 2 largest populated cities in Vietnam for the year 2025. Cancer incidence data from 2004 to 2013 collected from population-based cancer registries in these 2 cities were provided by Vietnam National Cancer Institute. Incidence cases in 2013 and the previous decades average annual percent changes of age-standardized cancer incidence rates combined with expected population growth were modeled to project cancer incidence for each cancer site by gender to 2025. A substantial double in cancer incidence from 2013 to 2025 resulted from a growing and aging population in HCMC and Hanoi. Lung, colorectum, breast, thyroid, and liver cancers, which represent 67% of the overall cancer burden, are projected to become the leading cancer diagnoses by 2025 regardless of genders. For men, the leading cancer sites in 2025 are predicted to be lung, colorectum, esophagus, liver, and pharynx cancer, and among women, they are expected to be breast, thyroid, colorectum, lung, and cervical cancer. We projected an epidemiological transition from infectious-associated cancers to a high burden of cancers that have mainly been attributed to lifestyle in both cities. We predicted that with 16.9% growth in the overall population and dramatic aging with these 2 urban centers, the burdens of cancer incidence will increase sharply in both cities over the next decades. Data on projections of cancer incidence in both cities provide useful insights for directing appropriate policies and cancer control programs in Vietnam.

Targeting EZH2 reactivates a breast cancer subtype-specific anti-metastatic transcriptional program.

Emerging evidence has illustrated the importance of epigenomic reprogramming in cancer, with altered post-translational modifications of histones contributing to pathogenesis. However, the contributions of histone modifiers to breast cancer progression are unclear, and how these processes vary between molecular subtypes has yet to be adequately addressed. Here we report that genetic or pharmacological targeting of the epigenetic modifier Ezh2 dramatically hinders metastatic behaviour in both a mouse model of breast cancer and patient-derived xenografts reflective of the Luminal B subtype. We further define a subtype-specific molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of the FOXC1 gene, thereby inactivating a FOXC1-driven, anti-invasive transcriptional program. We demonstrate that higher FOXC1 is predictive of favourable outcome specifically in Luminal B breast cancer patients and establish the use of EZH2 methyltransferase inhibitors as a viable strategy to block metastasis in Luminal B breast cancer, where options for targeted therapy are limited.