SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions.

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma.

Automatically Aligned and Environment-Friendly Twisted Stacking Terahertz Chiral Metasurface with Giant Circular Dichroism for Rapid Biosensing.

Chiral metasurfaces are capable of generating a huge superchiral field, which has great potential in optoelectronics and biosensing. However, the conventional fabrication process suffers greatly from time consumption, high cost, and difficult multilayer alignment, which hinder its commercial application. Herein, we propose a twisted stacking carbon-based terahertz (THz) chiral metasurface (TCM) based on laser-induced graphene (LIG) technology. By repeating a two-step process of sticking a polyimide film, followed by laser direct writing, the two layers of the TCM are aligned automatically in the fabrication. Laser manufacturing also brings such high processing speed that a TCM with a size of 15 × 15 mm can be prepared in 60 s. In addition, due to the greater dissipation of LIG than that of metals in the THz band, a giant circular dichroism (CD) of +99.5 to -99.6% is experimentally realized. The THz biosensing of bovine serum albumin enhanced by the proposed TCMs is then demonstrated. A wide sensing range (0.5-50 mg mL-1) and a good sensitivity [ΔCD: 2.09% (mg mL-1)-1, Δf: 0.0034 THz (mg mL-1)-1] are proved. This LIG-based TCM provides an environment-friendly platform for chiral research and has great application potential in rapid and low-cost commercial biosensing.

Multifunctional Motion Sensing Enabled by Laser-Induced Graphene.

The development of flexible sensors based on laser-induced graphene (LIG) has recently attracted much attention. It was commonly generated by laser-ablating commercial polyimide (PI). However, the weak mechanical extensibility of PI limits the development and diversified applications of LIG-based sensors. In this work, we adopted medical polyurethane (PU) tapes to peel off the LIG generated on PI and developed flexible and wearable sensors based on the proposed LIG/PU composite structure. Compared with other methods for LIG transfer, PU tape has many advantages, including a simplified process and being less time-consuming. We characterized the LIG samples generated under different laser powers and analyzed the property differences introduced by the transfer operation. We then studied the impact of fabrication mode on the strain sensitivity of the LIG/PU and optimized the design of a LIG/PU-based strain sensor, which possessed a gauge factor (GF) of up to 263.6 in the strain range of 75-90%. In addition, we designed a capacitive pressure sensor for tactile sensing, which is composed of two LIG/PU composite structures and a PI space layer. These LIG flexible devices can be used for human motion monitoring and tactile perception in sports events. This work provides a simple, fast, and low-cost way for the preparation of multifunctional sensor systems with good performance, which has a broad application prospect in human motion monitoring.

Complex network-based classification of radiographic images for COVID-19 diagnosis.

In this work, we present a network-based technique for chest X-ray image classification to help the diagnosis and prognosis of patients with COVID-19. From visual inspection, we perceive that healthy and COVID-19 chest radiographic images present different levels of geometric complexity. Therefore, we apply fractal dimension and quadtree as feature extractors to characterize such differences. Moreover, real-world datasets often present complex patterns, which are hardly handled by only the physical features of the data (such as similarity, distance, or distribution). This issue is addressed by complex networks, which are suitable tools for characterizing data patterns and capturing spatial, topological, and functional relationships in data. Specifically, we propose a new approach combining complexity measures and complex networks to provide a modified high-level classification technique to be applied to COVID-19 chest radiographic image classification. The computational results on the Kaggle COVID-19 Radiography Database show that the proposed method can obtain high classification accuracy on X-ray images, being competitive with state-of-the-art classification techniques. Lastly, a set of network measures is evaluated according to their potential in distinguishing the network classes, which resulted in the choice of communicability measure. We expect that the present work will make significant contributions to machine learning at the semantic level and to combat COVID-19.

RAB10 promotes breast cancer proliferation migration and invasion predicting a poor prognosis for breast cancer.

RAB10, a member of the small GTPase family, has complex biological functions, but its role in breast cancer (BC) remains unclear. The aim of this study was to investigate the relationship between RAB10's role in BC, its biological functions, and BC prognosis. An online database was used to analyze the correlation between differential expression of RAB10 in BC and prognosis. The results of immunohistochemical assays in clinical cohorts were combined with the database analysis. The chi-square test and COX regression were employed to analyze the correlation between RAB10 and pathological features of BC. MTT, Transwell, and wound healing assays were conducted to detect BC cell proliferation, invasion, and metastatic ability. Bioinformatics techniques were employed to explore the correlation between RAB10 and BC tumor immune cell infiltration, and to speculate the biological function of RAB10 in BC and related signaling pathways. Our findings suggest that RAB10 expression is elevated in BC and is associated with HER2 status, indicating a poor prognosis for BC patients. RAB10 can promote the proliferation, migration, and invasion ability of BC cells in vitro. RAB10 is also associated with BC immune cell infiltration and interacts with multiple signaling pathways. RAB10 is a potential biomarker or molecular target for BC.

Small-molecule MHC-II inducers promote immune detection and anti-cancer immunity via editing cancer metabolism.

Lack of MHC-II is emerging as a causal factor in cancer immune evasion, and the development of small-molecule MHC-II inducers is an unmet clinical need. Here, we identified three MHC-II inducers, including pristane and its two superior derivatives, that potently induce MHC-II expression in breast cancer cells and effectively inhibit the development of breast cancer. Our data suggest that MHC-II is central in promoting the immune detection of cancer to increase the tumor infiltration of T cells and enhance anti-cancer immunity. By discovering the malonyl/acetyltransferase (MAT) domain in fatty acid synthase (FASN) as the direct binding target of MHC-II inducers, we demonstrate that evasion of immune detection and cancer metabolic reprogramming are directly linked by fatty acid-mediated MHC-II silencing. Collectively, we identified three MHC-II inducers and illustrated that lack of MHC-II caused by hyper-activated fatty acid synthesis to limit immune detection is a potentially widespread mechanism underlying the development of cancer.

IRF4 as a novel target involved in malignant transformation of oral submucous fibrosis into oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) in the context of oral submucous fibrosis (OSF) has a high incidence owing to undefined pathogenesis. Identifying key genes and exploring the underlying molecular mechanisms involved in the conversion of OSF into OSCC are in urgent need. Differentially expressed genes (DEGs) between OSCC and OSF were dug from GEO databases and a total of 170 DEGs were acquired. Functional association of DEGs were analyzed by GO and KEGG. Protein-protein interactions (PPIs) analysis was carried out and candidate biomarkers were identified by Gene co-expression analysis and Cox analyses. Hub genes were confirmed by qRT-PCR in tissues and cell lines, of which we found that IRF4 mRNA was successively up-regulated from Normal to OSF and then to OSCC and associated with immune infiltrating levels. In addition, Immunohistochemical (IHC) and Immunofluorescence (IF) assays were conducted to validate the consistent upregulation of IRF4 and the oncogene role of IRF4 in OSF and OSCC at translation level. IRF4 may be indicative biomarker in transformation of OSF into OSCC. High IRF4 expression contribute to increased immune infiltration of OSCC and may provide a novel diagnostic marker for OSCC patients translated from OSF.

An electric molecular motor.

Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors1-3 that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane4,5, in which two cyclobis(paraquat-p-phenylene)6 (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet7,8, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by FOF1 ATP synthase9. The unidirectionality is powered by an oscillating10 voltage11,12 or external modulation of the redox potential13. Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound14 electric molecular motors.

Alternative transcribed 3' isoform of long non-coding RNA Malat1 inhibits mouse retinal oxidative stress.

The function of the cancer-associated lncRNA Malat1 during aging is as-of-yet uncharacterized. Here, we show that Malat1 interacts with Nucleophosmin (NPM) in young mouse brain, and with Lamin A/C, hnRNP C, and KAP1 with age. RNA-seq and RT-qPCR reveal a persistent expression of Malat1_2 (the 3'isoform of Malat1) in Malat1Δ1 (5'-1.5 kb deletion) mouse retinas and brains at 1/4th level of the full-length Malat1, while Malat1_1 (the 5'isoform) in Malat1Δ2 (deletion of 3'-conserved 5.7 kb) at a much lower level, suggesting an internal promoter driving the 3' isoform. The 1774 and 496 differentially expressed genes in Malat1Δ2 and Malat1Δ1 brains, respectively, suggest the 3' isoform regulates gene expression in trans and the 5' isoform in cis. Consistently, Malat1Δ2 mice show increased age-dependent retinal oxidative stress and corneal opacity, while Malat1Δ1 mice show no obvious phenotype. Collectively, this study reveals a physiological function of the lncRNA Malat1 3'-isoform during the aging process.

A brain-enriched lncRNA shields cancer cells from immune-mediated killing for metastatic colonization in the brain.

Brain metastases, including prevalent breast-to-brain metastasis (B2BM), represent an urgent unmet medical need in the care of cancer due to a lack of effective therapies. Immune evasion is essential for cancer cells to metastasize to the brain tissue for brain metastasis. However, the intrinsic genetic circuits that enable cancer cells to avoid immune-mediated killing in the brain microenvironment remain poorly understood. Here, we report that a brain-enriched long noncoding RNA (BMOR) expressed in B2BM cells is required for brain metastasis development and is both necessary and sufficient to drive cancer cells to colonize the brain tissue. Mechanistically, BMOR enables cancer cells to evade immune-mediated killing in the brain microenvironment for the development of brain metastasis by binding and inactivating IRF3. In preclinical brain metastasis murine models, locked nucleic acid-BMOR, a designed silencer targeting BMOR, is effective in suppressing the metastatic colonization of cancer cells in the brain for brain metastasis. Taken together, our study reveals a mechanism underlying B2BM immune evasion during cancer cell metastatic colonization of brain tissue for brain metastasis, where B2BM cells evade immune-mediated killing in the brain microenvironment by acquiring a brain-enriched long noncoding RNA genetic feature.

Electron-catalysed molecular recognition.

Molecular recognition1-4 and supramolecular assembly5-8 cover a broad spectrum9-11 of non-covalently orchestrated phenomena between molecules. Catalysis12 of such processes, however, unlike that for the formation of covalent bonds, is limited to approaches13-16 that rely on sophisticated catalyst design. Here we establish a simple and versatile strategy to facilitate molecular recognition by extending electron catalysis17, which is widely applied18-21 in synthetic covalent chemistry, into the realm of supramolecular non-covalent chemistry. As a proof of principle, we show that the formation of a trisradical complex22 between a macrocyclic host and a dumbbell-shaped guest-a molecular recognition process that is kinetically forbidden under ambient conditions-can be accelerated substantially on the addition of catalytic amounts of a chemical electron source. It is, therefore, electrochemically possible to control23 the molecular recognition temporally and produce a nearly arbitrary molar ratio between the substrates and complexes ranging between zero and the equilibrium value. Such kinetically stable supramolecular systems24 are difficult to obtain precisely by other means. The use of the electron as a catalyst in molecular recognition will inspire chemists and biologists to explore strategies that can be used to fine-tune non-covalent events, control assembly at different length scales25-27 and ultimately create new forms of complex matter28-30.

FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance by stabilizing ELAVL1 protein and regulating downstream Rab10/TLR4 pathway.

BACKGROUND: Breast cancer (BC) is one of the most common cancers and the leading cause of death in women. Previous studies have demonstrated that FAM49B is implicated in several tumor progression, however, the role and mechanism of FAM49B in BC remain to be explored. Therefore, in this study, we aimed to systematically study the role of FAM49B in the proliferation, metastasis, apoptosis, and chemoresistance of BC, as well as the corresponding molecular mechanisms and downstream target. METHODS: The ONCOMINE databases and Kaplan-Meier plotter databases were analyzed to find FAM49B and its prognostic values in BC. FAM49B expression in BC and adjacent non-tumor tissues was detected by western blot and IHC. Kaplan-Meier analysis was used to identify the prognosis of BC patients. After FAM49B knockdown in MCF-7 and MDA-MB-231 cells, a combination of co-immunoprecipitation, MTT, migration, and apoptosis assays, nude mouse xenograft tumor model, in addition to microarray detection and data analysis was used for further mechanistic studies. RESULTS: In BC, the results showed that the expression level of FAM49B was significantly higher than that in normal breast tissue, and highly expression of FAM49B was significantly positively correlated with tumor volume, histological grade, lymph node metastasis rate, and poor prognosis. Knockdown of FAM49B inhibited the proliferation and migration of BC cells in vitro and in vivo. Microarray analysis revealed that the Toll-like receptor signaling pathway was inhibited upon FAM49B knockdown. In addition, the gene interaction network and downstream protein validation of FAM49B revealed that FAM49B positively regulates BC cell proliferation and migration by promoting the Rab10/TLR4 pathway. Furthermore, endogenous FAM49B interacted with ELAVL1 and positively regulated Rab10 and TLR4 expression by stabilizing ELAVL1. Moreover, mechanistic studies indicated that the lack of FAM49B expression in BC cells conferred more sensitivity to anthracycline and increased cell apoptosis by downregulating the ELAVL1/Rab10/TLR4/NF-κB signaling pathway. CONCLUSION: These results demonstrate that FAM49B functions as an oncogene in BC progression, and may provide a promising target for clinical diagnosis and therapy of BC.

Comprehensive Analysis of Innate Immunophenotyping Based on Immune Score Predicting Immune Alterations and Prognosis in Breast Cancer Patients.

Breast cancer is the most common cancer, with the highest mortality rate and the most diagnosed cancer type in women worldwide. To identify the effect innate immune checkpoint for breast cancer immunotherapy, the innate immune prognostic biomarkers were selected through the ICI score model and the risk model in breast cancer patients. Moreover, the reliability and accuracy of the ICI score model and the risk model were further examined through the analysis of breast cancer prognosis and immune cell infiltration. The pan cancer analysis further confirmed and selected CXCL9 as the key innate immune checkpoint for breast cancer immunotherapy and identified three small molecular drugs for target CXCL9 through molecular docking analysis. In summary, CXCL9 significantly correlated with the prognostic of breast cancer and immune cell infiltration and could be innate immune checkpoint for breast cancer immunotherapy.

Enhanced terahertz focusing for a graphene-enabled active metalens.

Graphene-based terahertz (THz) metasurfaces have the advantages of ultra-small thickness, electrical tunability, and fast tuning speed. However, many such structures suffer low efficiency, especially for transmissive devices. Here we propose a hybrid structure for focusing THz waves with tunability and enhanced focusing efficiency, which is composed of a graphene-loaded metallic metasurface sandwiched by two mutually orthogonal gratings. Experimental results show that due to the multi-reflection between the metasurface layer and the grating layer, the focusing efficiency is enhanced by 1.8 times, and the focal length of the metalens is increased by 0.61 mm when the applied gate voltage on the graphene is increased from 0 V to 1.4 V. We hope the proposed structure may open a new avenue for reconfigurable THz metasurfaces with high efficiencies.

Clinical Characteristics of Testicular Torsion and Identification of Predictors of Testicular Salvage in Children: A Retrospective Study in a Single Institution.

PURPOSE: Testicular torsion (TT) is a serious surgical emergency. Prompt diagnosis and treatment of TT are essential to improve the incidence of salvaged testes. The aim of this study was to evaluate the historical features, physical examination findings, laboratory tests, and ultrasound examinations in children with TT, as well as to identify the predictors of testicular salvage in children. MATERIALS AND METHODS: We retrospectively reviewed the records of 136 males who presented with TT to our institution. Clinical findings, physical examinations, laboratory data, color Doppler ultrasound findings, operating results, and the results of follow-up were collected and analyzed. Patients with neonatal torsion, negative scrotal exploration, or testicular appendix torsion were excluded. A multivariable logistic regression model was used to identify predictors of testicular salvage. Receiver operator characteristics analyses were performed to determine the probability of a non-salvageable torsed testis based on time and degree of twisting. RESULTS: A total of 136 children with TT were identified. Patients were aged from 1 to 16 years, with a mean age of 9.7 years (median, 12; range, 1-16 years). The peak incidences of TT were found between ages of 12 and 14 years. Acute TT is significantly more common in the winter. Testicular salvage occurred in 49 (36%) cases. Of the 49 cases of testicular salvage, 5 patients developed subsequent testicular atrophy. Cutoff values of 13.5 h and 530 degrees of torsion would provide sensitivities of 96 and 61%, with specificity of 80 and 70%, respectively. Multivariate analysis showed that time to surgery and degree of testicular twist were correlated with the risk of a non-salvageable testis. CONCLUSIONS: Testicular salvage can be predicted by the duration of symptoms along with degree of twisting. Early scrotal exploration based on careful physical examination decreases the risk of misdiagnosis of spermatic cord torsion. A certain percentage of children with TT presenting with lower abdominal pain should have their testicles checked to make sure that they do not have torsion, especially those visitors in cold season.

Electrochemical Switching of a Fluorescent Molecular Rotor Embedded within a Bistable Rotaxane.

We report how the nanoconfined environment, introduced by the mechanical bonds within an electrochemically switchable bistable [2]rotaxane, controls the rotation of a fluorescent molecular rotor, namely, an 8-phenyl-substituted boron dipyrromethene (BODIPY). The electrochemical switching of the bistable [2]rotaxane induces changes in the ground-state coconformation and in the corresponding excited-state properties of the BODIPY rotor. In the starting redox state, when no external potential is applied, the cyclobis(paraquat-p-phenylene) (CBPQT4+) ring component encircles the tetrathiafulvalene (TTF) unit on the dumbbell component, leaving the BODIPY rotor unhindered and exhibiting low fluorescence. Upon oxidation of the TTF unit to a TTF2+ dication, the CBPQT4+ ring is forced toward the molecular rotor, leading to an increased energy barrier for the excited state to rotate the rotor into the state with a high nonradiative rate constant, resulting in an overall 3.4-fold fluorescence enhancement. On the other hand, when the solvent polarity is high enough to stabilize the excited charge-transfer state between the BODIPY rotor and the CBPQT4+ ring, movement of the ring toward the BODIPY rotor produces an unexpectedly strong fluorescence signal decrease as the result of photoinduced electron transfer from the BODIPY rotor to the CBPQT4+ ring. The nanoconfinement effect introduced by mechanical bonding can effectively lead to modulation of the physicochemical properties as observed in this bistable [2]rotaxane. On account of the straightforward synthetic strategy and the facile modulation of switchable electrochromic behavior, our approach could pave the way for the development of new stimuli-responsive materials based on mechanically interlocked molecules for future electro-optical applications, such as sensors, molecular memories, and molecular logic gates.

Highly Stable Organic Bisradicals Protected by Mechanical Bonds.

Two new highly charged [2]catenanes-namely, mHe[2]C·6PF6 and mHo[2]C·6PF6-were synthesized by exploiting radical host-guest templation between derivatives containing BIPY•+ radical cations and the meta analogue of cyclobis(paraquat-p-phenylene). In contrast to related [2]catenanes that have been isolated as air-stable monoradicals, both mHe[2]C·6PF6 and mHo[2]C·6PF6 exist as air-stable singlet bisradicals, as evidenced by both X-ray crystallography in the solid state and EPR spectroscopy in solution. Electrochemical studies indicate that the first two reduction peaks of these two [2]catenanes are shifted significantly to more positive potentials, a feature which is responsible for their extraordinary stability in air. The mixed-valence nature of the mono- and bisradical states endows them with unique NIR absorption properties, e.g., NIR absorption bands for the mono- and bisradical states observed at ∼1800 and ∼1450 nm, respectively. These [2]catenanes are potentially useful in applications that include NIR photothermal conversion, UV-vis-NIR multiple-state electrochromic materials, and multiple-state memory devices. Our findings highlight the principle of "mechanical-bond-induced stabilization" as an efficient strategy for designing persistent organic radicals.

Gate-controlled terahertz focusing based on graphene-loaded metasurface.

Metasurfaces have proven their great application potentials in terahertz (THz) wave modulations. However, realizing an active metasurface retaining lensing functionality in the THz frequency regime is still highly desired. Here a metalens, featuring electrically tunable focal length, based on propagation phase delay, is proposed and demonstrated experimentally. To have full control over the designed lens functionality, a gold thin film etched with a C-shaped aperture antenna array covered by monolayer graphene is used. By applying a bias voltage to the graphene, the phase control of the antenna array is changed, and thus the focus of the linearly polarized THz beam can be flexibly tuned from 7.13mm to 8.25mm. The proposed approach has a promising perspective for a variety of applications in communication, reconfigurable flat optics and real-time imaging in THz regime.

ERK1 indicates good prognosis and inhibits breast cancer progression by suppressing YAP1 signaling.

The mitogen-activated protein kinase/extracellular signal-regulated (MAPK/ERK) pathway is a well-characterized signaling pathway during the development of various cancer types. ERK1 and ERK2, the two kinase effectors of MAPK cascade, exhibit high similarity. However, it is still unknown whether these two kinases are functionally different or in contrast functionally redundant during the development of breast cancer. We found that ERK1 expression levels were significantly lower in basal breast cancer compared with luminal breast cancer and normal breast tissues. RNA sequencing data suggested that ERK1 was associated with Hippo signaling pathway and cell proliferation in breast cancer cells. The gene set enrichment analysis (GSEA) further showed enrichment for YAP1 signaling pathway in breast cancer cell lines and tumors with low expression of ERK1. Silencing of ERK1 elevated YAP1 expression and TEAD activity in breast cancer cells. Additionally, ERK1 inhibited breast cancer cell proliferation via regulation of YAP1. The Kaplan-Meier analysis of data in patients with breast cancer suggested that, higher expression of ERK1 was associated with better prognosis, whereas, higher expression of ERK2 predicted poorer prognosis. These findings unveiled the role of ERK1 on regulation of YAP1 signaling pathway, indicating ERK1 as a negative regulator of breast cancer progression.

TUFT1 promotes metastasis and chemoresistance in triple negative breast cancer through the TUFT1/Rab5/Rac1 pathway.

BACKGROUND: Triple negative breast cancer (TNBC) is a breast cancer (BC) subtype that is characterized by its strong invasion and a high risk of metastasis. However, the specific mechanisms underlying these phenotypes are unclear. TUFT1 plays an important role in BC and impacts the proliferation and survival of BC cells. Recent studies have shown that TUFT1 mediates intracellular lysosome localization and vesicle transport by regulating Rab GTPase, but the relevance of this activity in TNBC is unknown. Therefore, our aim was to systematically study the role of TUFT1 in the metastasis and chemoresistance of TNBC. METHODS: We measured TUFT1, Rab5-GTP, and Rac1-GTP expression levels in samples of human TNBC by immunohistochemistry (IHC) and conducted univariate and multivariate analyses. shRNA-mediated knockdown and overexpression, combined with transwell assays, co-immunoprecipitation, a nude mouse xenograft tumor model, and GTP activity assays were used for further mechanistic studies. RESULTS: TUFT1 expression was positively correlated with Rab5-GTP and Rac1-GTP in the TNBC samples, and co-expression of TUFT1 and Rab5-GTP predicted poor prognosis in TNBC patients who were treated with chemotherapy. Mechanism studies showed that TUFT1 could activate Rab5 by binding to p85α, leading to activation of Rac1 through recruitment of Tiam1, and concurrent down-regulation of the NF-κB pathway and proapoptotic factors, ultimately promoting metastasis and chemoresistance in TNBC cells. CONCLUSIONS: Our findings suggest that the TUFT1/Rab5/Rac1 pathway may be a potential target for the effective treatment of TNBC.