scholarly journals Progress in the research of p53 tumour suppressor activity controlled by Numb in triple‐negative breast cancer

2020 ◽  
Vol 24 (13) ◽  
pp. 7451-7459
Author(s):  
Jie Xian ◽  
Yu Cheng ◽  
Xue Qin ◽  
Yijia Cao ◽  
Yetao Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumour Suppressor ◽  
Suppressor Activity ◽  
Tumour Suppressor Activity

scholarly journals ROLE OF TUMOUR SUPPRESSOR GENE P53 IN TRIPLE NEGATIVE BREAST CANCER

2017 ◽  
Vol 5 (4.2) ◽  
pp. 4585-4589
Author(s):  
Priya S Patil ◽  
◽  
Jaydeep N Pol ◽  
Ashalata D Patil ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor

scholarly journals Diverse Roles of Annexin A6 in Triple-Negative Breast Cancer Diagnosis, Prognosis and EGFR-Targeted Therapies

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1855 ◽  
Author(s):  
Olga Y. Korolkova ◽  
Sarrah E. Widatalla ◽  
Stephen D. Williams ◽  
Diva S. Whalen ◽  
Heather K. Beasley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Kinase Inhibitors ◽  
Triple Negative ◽  
Acquired Resistance ◽  
Breast Cancer Diagnosis ◽  
Scaffolding Protein ◽  
Poor Overall Survival ◽  
Suppressor Activity

The calcium (Ca2+)-dependent membrane-binding Annexin A6 (AnxA6), is a multifunctional, predominantly intracellular scaffolding protein, now known to play relevant roles in different cancer types through diverse, often cell-type-specific mechanisms. AnxA6 is differentially expressed in various stages/subtypes of several cancers, and its expression in certain tumor cells is also induced by a variety of pharmacological drugs. Together with the secretion of AnxA6 as a component of extracellular vesicles, this suggests that AnxA6 mediates distinct tumor progression patterns via extracellular and/or intracellular activities. Although it lacks enzymatic activity, some of the AnxA6-mediated functions involving membrane, nucleotide and cholesterol binding as well as the scaffolding of specific proteins or multifactorial protein complexes, suggest its potential utility in the diagnosis, prognosis and therapeutic strategies for various cancers. In breast cancer, the low AnxA6 expression levels in the more aggressive basal-like triple-negative breast cancer (TNBC) subtype correlate with its tumor suppressor activity and the poor overall survival of basal-like TNBC patients. In this review, we highlight the potential tumor suppressor function of AnxA6 in TNBC progression and metastasis, the relevance of AnxA6 in the diagnosis and prognosis of several cancers and discuss the concept of therapy-induced expression of AnxA6 as a novel mechanism for acquired resistance of TNBC to tyrosine kinase inhibitors.

scholarly journals The research progress of p53 tumour suppressor activity controlled by Numb in triple-negative breast cancer

2018 ◽  
Author(s):  
Jie Xian ◽  
Yu Cheng ◽  
Xue Qin ◽  
Yequn Luo ◽  
Yijia Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Fate ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Research Progress ◽  
Epithelial Cell Line ◽  
Mrna Levels ◽  
Suppressor Activity ◽  
Cell Fractions

AbstractNumb is known as a cell fate determinant as it determines the direction of cell differentiation by asymmetrically partitioning at mitosis. It has been shown to be a tumor suppressor, and there is frequent loss of Numb expression in breast cancer. Numb enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. The aim of this study was to investigate the expression and migration of Numb, HDM2 and p53 proteins in the membrane, cytoplasmic and nuclear fractions of MCF-10A cells and MDA-MB-231 cells. We extracted the cell fractions to detect changes of these three protein levels after re-expression of NUMB in the basal-like triple-negative cell line MDA-MB-231 and knocking down NUMB in the normal mammary epithelial cell line MCF-10A. Our results show that Numb protein can migrate from cytoplasm to nucleus of the MDA-MB-231 cells. Numb protein regulates p53 levels in nucleus of MCF-10A cells and MDA-MB-231 cells, and the Numb levels is positively correlated with p53 levels. We have a finding on HDM2 protein that after knocking down NUMB in MCF-10A cells, it was remarkably reduced in the membrane fraction of NUMB knockdown cells, but its mRNA levels was significantly increased. We also examined the Numb expression in 125 patients with triple-negative breast cancer, 61(48.8%) displayed deficient or reduced expression of Numb. The percent of Ki67>14% in retained Numb group was significantly lower than that in the reduced and deficient Numb group (86.00% vs. 98.40%, P=0.0171).

NFKBIA deletion in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1012-1012 ◽  
Author(s):  
Markus Bredel ◽  
Hyunsoo Kim ◽  
Nanda K. Thudi ◽  
Denise M. Scholtens ◽  
James A. Bonner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Target Genes ◽  
Triple Negative ◽  
Lung Metastases ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Breast Cancers ◽  
Suppressor Activity ◽  
Free Survival

1012 Background: While effective, target-directed therapies are available for ER-positive and HER2-amplified breast cancer, adjuvant therapeutic options for triple-negative breast cancer (TNBC) are limited in the absence of well-defined molecular targets. Constitutive activation of oncogenic nuclear factor kB (NFkB) has been associated with ER-negative or basal-like (BL) breast cancers, but the underlying mechanism of this activation remains undefined. We previously showed that deletion of the endogenous NFkB repressor gene NFKBIA associates with EGFR non-amplified glioblastoma multiforme and portends unfavorable clinical outcome (Bredel et al. NEJM 2011). Methods: We analyzed >5,000 human breast cancers for deletions, mutations and/or expression of NFKBIA. We studied tumor suppressor activity of NFKBIA and the effect of targeted NFkB inhibition in cell culture with various NFKBIA genotypes. We compared molecular results with outcomes of affected persons. Results: NFKBIA is often (10.8%) deleted but not mutated in breast cancer. NFKBIA deletions are significantly associated with TNBC (32.8%) and particularly frequent in the BL subtype (36.7%). Loss of NFKBIA exerts a haploinsufficient effect on NFKBIA expression and the transactivation of several NF-kB target genes with important roles in breast carcinogenesis. Restoration of NFKBIA expression or pharmacologic NFkB inhibition attenuates the malignant phenotype of cells cultured from TNBC with NFKBIA deletion. Deletion and low expression of NFKBIA are highly associated with unfavorable overall survival, independent of patient age, tumor stage, nodal status, and tumor subtype. Loss of NFKBIA expression portends significantly poorer disease-specific survival, recurrence-free survival, and distant metastasis-free survival. Moreover, NFKBIA expression is significantly associated with duration of metastasis-free survival in subgroups of patients with brain or lung metastases from breast cancer. Conclusions: NFKBIA is a new, prognostically relevant, molecular target in TNBC, which remains a clinically challenging subtype of breast cancer with limited treatment options.

Identification of new therapeutic leads for triple negative breast cancer subtypes

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
AJ Robles ◽  
L Du ◽  
S Cai ◽  
RH Cichewicz ◽  
SL Mooberry
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes ◽  
Therapeutic Leads
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