HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

miR-17-5p regulates proliferation, invasion, migration and apoptosis of nasopharyngeal carcinoma CNE2 cells by down-regulating BRMS1Lexpression / 中国肿瘤生物治疗杂志

@# Objective: To explore the molecular mechanism of miR-17-5p regulating the proliferation and invasion of nasopharyngeal carcinoma cells by regulating the expression of breast cancer metastasis suppressor 1 like (BRMS1-like or BRMS1L) gene. Methods:A total of 40 cases of nasopharyngeal carcinoma tissues and corresponding paracancerous tissues resected from nasopharyngeal carcinoma patients, who were admitted to the General Hospital of Pingdingshan Shenma Medical Group during January 2014 to December 2017, were included in this study; in addition, nasopharyngeal carcinoma cell lines CNE 2, HONE 1, C666-1 and nasopharyngeal immortalized epithelial cell line NP69 were also collected for this study. The expression of miR-17-5p in nasopharyngeal carcinoma tissues and cell lines was detected by qPCR. The targeted relationship between BRMS1L and miR-17-5p was predicted by the StarBase and verified by the Dual luciferase reporter gene assay. Effects of transfection of miR-17-5p mimics and inhibitors on the expression of BRMS1Lin CNE2 cells were detected by WB assay. CCK-8, Transwell and Flow cytometry were used to detect the effects of miR-17-5p/BRMS1L axis on the proliferation, migration, invasion and apoptosis of CNE 2 cells. Results: miR-17-5p was highly expressed in nasopharyngeal carcinoma tissues and cell lines (P<0.05 or P<0.01). Knockdown of miR-17-5p significantly inhibited proliferation, invasion and migration of CNE2 cells but promoted apoptosis (P<0.05 or P<0.01); miR-17-5p targeted BRMS1Land down-regulated its expression. Over-expression of BRMS1Lsignificantly inhibited the proliferation, invasion and migration of CNE2 cells but promoted apoptosis (all P<0.01); while simultaneous over-expression of miR-17-5p and BRMS1L reversed the above effects (all P<0.01). Conclusion: miR-17-5p promoted proliferation, invasion, migration and inhibited apoptosis of CNE 2 cells by down-regulating the expression of BRMS1L.

Contralateral Internal Mammary Lymphadenopathy Mimicking Metastasis in a Patient with a History of Breast Cancer and Prior Interstitial Mammoplasty by Paraffin Injection: MRI, PET-CT, and Pathological Findings

Foreign body injections into breasts may produce foreign body reactions, fibrosis, and local swelling of involved lymph nodes, which can be misdiagnosed as metastasis or malignancy. Here, the authors report MR imaging, PET-CT imaging, and pathologic findings of contralateral internal mammary lymphadenopathy suspicious of breast cancer metastasis in a 58-year-old woman with history of left breast cancer, and previous interstitial mammoplasty by paraffin injection in both breasts.

Breast cancer metastasis suppressor gene 1 correlates with progression of cancer: a Meta-analysis / 国际肿瘤学杂志

Objective To evaluate the association between the expression of breast cancer metastasis suppressor gene 1 (BRMS1) and the progression of cancer,and provide the basis for predicting the occurrence and metastasis of cancer.Methods Articles about BRMS1 with the clinical research literatures of cancer from PubMed,EMBase,China National Knowledge Infrastructure,Wanfang and VIP database were retrieved.The association between the expression of BRMS1 and tumorigenesis was evaluated by odds ratio (OR).The RevMan 5.3 software was used to complete the meta-analysis.Results A total of 27 articles were included,involving 2 282 cases in cancer group and 1 236 cases in the control group.The meta-analysis results showed that BRMS1 expression was significantly upregulated in cancer lesions compared with paired non-cancer (OR =0.10,95％ CI:O.08-0.14,Z =15.37,P ＜0.000 O1).In the subgroup about the type of cancers,there was statistically significant difference in the pooled OR between breast cancer and the control group (OR =0.10,95％ CI:0.05-0.20,Z =6.18,P ＜ 0.000 01).Conclusion The level of BRMS1 is negatively correlated with tumorigenesis including breast cancer.Low or absent BRMS1 expression in the tumor tissue may be an adverse predictive factor of tumorigenesis and metastasis.

Mechanism of breast cancer metastasis suppressor gene 1 inhibiting tumor metastasis / 国际肿瘤学杂志

Breast cancer metastasis suppressor gene 1 (BRMS1) significantly reduces the invasion and metastasis of cancer cells.BRMS1 gene expression is decreased or deleted in the cells of various malignant tumors.BRMS1 gene can inhibit tumor cells invasion and metastasis by means of regulating gene transcription and protein translation by phosphoinositide signaling and nuclear factor-κB (NF-κB) signaling pathways,repairing intercellular communication and interacting with the mSin3-histone deacetylase (HDAC) complex,estrogen receptor and other proteins.BRMS1 gene may be a new target for the gene treatment of tumor metastasis.

Clinical, pathological features and treatment of metastatic breast cancer with triple negative breast cancer and its relationship with disease free survival / 中国综合临床

Objective To study the clinical,pathological features and treatment of metastatic breast cancer with triple negative breast cancer(TNBC) and its relationship with disease free survival.Methods One hundred and fifty-eight cases of TNBC patients who were treated in the First Affiliated Hospital of Zhengzhou University and the Chinese Medicine Hospital of Changge from January 2004 to January 2009 were selected as the research objects.All patients received operation and radiotherapy,the relationship between the clinical characteristics,pathological features and treatment with 5,3 year survival rate,and the recurrence and metastasis of patient were analyzed.Results In clinical stage Ⅲ period,the 3 years survival rate was 46.51％ (20/43),5years survival rate was 37.21％ (16/43),all significantly lower than in the phase Ⅰ and Ⅱ (91.53％ (54/59) and 76.27 ％ (45/59);87.50％ (49/56) and 71.43 ％ (40/56)),and the differences were statistically significant (x2=25.306,15.787,19.348,11.592;P＜0.001).With lymph node metastasis,the 3 years survival rate was 66.00％ (33/50),5 years survival rate was 50.00％ (25/50),significantly lower than that without lymph node metastasis(83.33％ (90/108),70.37％ (76/108)),the difference was statistically significant (x2=5.954,6.150;P＜0.05).In pathological grade Ⅲ,the 3 years survival rate was 65.67％(44/67),5 years survival rate was 43.28％ (29/67),significantly lower than that of grade Ⅰ (92.86％ (26/28),85.71％ (24/28)) and grade Ⅱ (84.13％ (53/63),76.19％ (48/63)),the difference was statistically significant(x2=7.527,14.414,5.839,14.560;P＜0.05).The 3 year survival rate of radiotherapy group was significantly higher than that in non radiotherapy group,the difference was statistically significant (81.58％ (31/38) vs.57.69％ (15/26);x2=4.357,P＜0.05).Patients with metastatic sites were lung,liver,brain,bone and supraclavicular lymph nodes,the median survival time after the transfer all more than 2 years.Conclusion TNBC is a special type of breast cancer that is difficult to treat,no consensus has been reached on the clinical treatment plan.Breast conserving surgery also has certain application value,radiotherapy only can increase the 3 year survival rate.The clinical stage and pathological grade are the influence factors of prognosis.

Detection of breast cancer metastasis-related genes by co-word analysis and network analysis / 中华医学图书情报杂志

Objective To provide the reference for early diagnosis and treatment of breast cancer by detecting its metastasis-related genes.Methods Breast cancer metastasis-related genes were searched from PubMed-covered papers with their conception matched according to the MetaMap.A gene-gene matrix was generated using data a-nalysis software.An interaction network of breast cancer metastasis-related genes was established using Ucinet 6 and its related indexes were analyzed.Results tp53, thra, erbb2, esr1, cdh1, egfr, nr4al and cd69 were the core genes for breast cancer metastasis.Conclusion Co-word analysis can show breast cancer metastasis-related genes. However, the role of cd69 in breast cancer metastasis remains unclear and is thus necessary to be further confirmed.

Abnormal expression of BRMS1 and Cx43 protein in thyroid cancer occurrence and progression / 中国肿瘤临床

Objective:To investigate the protein expression levels of breast cancer metastasis suppressor 1 (BRMS1) and Con-nexin 43 (Cx43) in thyroid cancer and their correlation with clinicopathologic parameters. Methods:Immunohistochemistry Streptavi-din-Peroxidase method was used to detect the BRMS1 and Cx43 protein expression in 195 tissue samples, including 90 cases with thy-roid carcinoma, 45 cases with thyroid adenoma, 30 cases with nodular goiter, and 30 cases with normal thyroid glands. Results:The positive rates of BRMS1 and Cx43 expression was 56.7%(51/90) and 41.1%(37/90) in thyroid carcinoma, respectively, which are sig-nificantly lower than the rates in thyroid adenoma, nodular goiter, and normal thyroid gland tissues (P<0.001). Of the three pathological types of thyroid cancer, the positive expression rate of Cx43 was 61.9%in papillary carcinoma, 27.8%in medullary carcinoma, 27.3%in follicular carcinoma, and 12.5%in undifferentiated carcinoma. Statistical differences in the BRMS1 expression among papillary car-cinoma and the other pathological types were also noted. Unlike the patients without lymph node metastasis, the positive expression of BRMS1 and Cx43 proteins were both significantly low among patients suffering from nodal metastasis. Subgroup analysis shows that the positive expression of BRMS1 and Cx43 protein gradually decreased with TNM staging. In addition, a positive correlation was ob-served between the BRMS1 and Cx43 protein expression (r=0.494, P=0.032). Conclusion:The decreased expression of BRMS1 and Cx43 proteins is significantly correlated with the metastasis of thyroid cancer and malignant grade. The combined detection of the two proteins can be ideal biomarkers for judging the prognosis of thyroid carcinoma.

"""Yang transforming Qi, Yin constituting the body""theory in the treatment of breast cancer metastasis" / 国际中医中药杂志

The use ofYang transforming Qi, Yin constituting the bodycan be used in the treatment of metastasis of breast cancer from pathogenesis transformation view. Based on literature, this article analyzed the theory of Yang transforming Qi, Yin constituting the body and its possible guidance to clinical practice. Then the article illustrated the application cases of this theory in the treatment of breast cancer metastasis.

Effect of BRMS1 on the invasion and metastasis of ovarian cancer cells by RNA interference / 肿瘤研究与临床

Objective To study the effect of BRMS1 on the invasion and metastasis of ovarian cancer cells. Methods BRMS1 small interfering RNA (BRMS1-siRNA) was transfected into human ovarian cancer cell-line OVCAR3 by liposome transfection method. The cells were divided into 3 groups: experimental group with BRMSl-siRNA, negative control group with siRNA that did not impact any gene, blank control group without any transfection. Changes of invasion and migration in the cells were per-formed using transwell invasion and migration assay. Results BRMS1 gene was silenced in OVCAR3 cell line successfully detecting by quantitative real-time RT-PCR and immunoblotting.In transwell invasion assay,the numbers of cells in lower chamber passing through the membrane in transfected group were more than negative control group and blank control group (190±8.5, 144±7.8 and 146±6.8 respectively) (t=8.747, t=8.869, P=0.000), while in transwell migration assay, the numbers of cells in lower chamber passing through the membrane in transfected group were more than negative control group and blank control group were (231 ±8.9, 177±9.7 and 182±7.9 respectively) (t=9.314, t=9.224, P=0.000), both with significant differences among the 3 groups. Conclusion BRMS1 gene could suppress the invasion and metastasis of ovarian cancer cells.

Effect of breast cancer metastasis suppressor gene 1 on the migration of breast cancer cells / 肿瘤

Objective: To study the effect of breast cancer metastasis suppressor gene 1 (BRMS1) on the migration of human breast cancer cells. Methods: An eukaryotic expression vector containing BRMS1 was constructed and was transfected into human breast cancer MDA-MB-231-HM cells by using Lipofectin 2000. Expression of BRMS1 mRNA was detected by real-time PCR. The migration of the cells was assayed by Transwell test. Meanwhile, three pairs of siRNA targeting BRMS1 were designed. The most effective siRNA was screened by real-time PCR and transfected into MDA-MB-231 cells. The migration ability of the transfected cells was detected. Results: Compared with the cells transfected with empty vector, the number of MDA-MB-231-HM cells on the underlayer of transwell decreased by 51.9% after stably transfected with BRMS1. One pair of siRNA was selected which could notably down-regulated BRMS1 expression at mRNA level. After siRNA transfection, the number of MDA-MB-231 cells on the underlayer of transwell increased by 17.9%. Conclusion: BRMS1 suppresses the migration of breast cancer cells, which indicates that BRMS1 may suppress cancer distant metastasis by inhibiting migration of breast cancer cells.

Suppressing Function of Breast Cancer Metastasis Suppressor 1 in Breast Cancer Metastasis / 中国普外基础与临床杂志

Objective To review the recent studies on the suppressing function of breast cancer metastasis suppressor 1 (BRMS1) in breast cancer metastasis. Methods The recent literatures on the mechanisms of BRMS1 in the breast cancer that were published in and abroad were reviewed and summarized. Results BRMS1, similar to the other anti-metastasis genes, only suppresses the metastasis of breast cancer cells but has nothing to do with the growth of tumor. BRMS1 could suppress metastasis of tumor cells by reestablishing both the homospecific and the heterospecific gap junctional intercellular comminications (GJIC) and by altering the expressions of relevant metastasis genes in the breast cancer. Conclusion Further studies on BRMS1 may be helpful to understand the metastasis of breast cancer, which may provide a new way for the diagnosis and treatment of breast cancer.