scholarly journals Expression of metastasis suppressor BRMS1 in breast cancer cells results in a marked delay in cellular adhesion to matrix

2013 ◽  
Vol 53 (12) ◽  
pp. 1011-1026 ◽  
Author(s):  
Yekaterina B. Khotskaya ◽  
Benjamin H. Beck ◽  
Douglas R. Hurst ◽  
Zhenbo Han ◽  
Weiya Xia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cellular Adhesion ◽  
Metastasis Suppressor

scholarly journals The RhoGAP Protein DLC-1 Functions as a Metastasis Suppressor in Breast Cancer Cells

2005 ◽  
Vol 65 (14) ◽  
pp. 6042-6053 ◽  
Author(s):  
Steve Goodison ◽  
Jing Yuan ◽  
Derek Sloan ◽  
Ryung Kim ◽  
Cheng Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastasis Suppressor

scholarly journals The Effects of CD82 Palmitoylation on the Metabolic Pathways of EGFR and c-Met in Breast Cancer Cells and their Molecular Mechanisms

2021 ◽  
Author(s):  
Jingya Bu ◽  
Weiliang Zhong ◽  
Meixian Li ◽  
Shuiqing He ◽  
Mingzhe Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Metabolic Pathways ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Metastasis Suppressor ◽  
Recycling Endosome ◽  
Palmitoylation Site

Abstract Background: As a tumor metastasis suppressor, tetraspanin CD82 is reduced in many malignant tumors and often affects the composition of tumor microenvironment by changing the heterogeneity of cell membrane. EGFR or c-Met signaling pathway can regulate the metastasis ability of tumor cells and participate in the formation of tetraspanin web. The study of CD82 palmitoylation modification and metabolic pathway of tumor related molecules in tumor cells is still incomplete. This article focuses on studying the expression and distribution of EGFR and c-Met in cancer cells as well as related metabolic pathways and their molecular mechanisms after studying different palmitoylation site mutations.Methods: Western blot and immunofluorescence methods were used to detect the distribution of EGFR in breast cancer MDA-MB-231 cells after different CD82 palmitoylation site mutations. Then use the immunoprecipitation method to determine the interaction relationship between the molecules and the molecular mechanism.Results: We found that when CD82 combined with palmitoylation mutation at Cys5+Cys74 can enhance the internalization of EGFR, but has no effect on the expression and location of c-Met. When CD82 is combined with palmitoylation mutation at the Cys5+Cys74 site, with the assistance of tubulin, EGFR is internalized and strengthened by direct binding to CD82 and a large number of localizations on the recycling endosome. By forming the EGFR/CD82/Rab11a/FIP2 complex, it is metabolized through the circulation pathway, and re-expression of EGFR and CD82 on the cell membrane.Conclusions: From our results, we can demonatrate that CD82 palmitoylation mutation can change the distribution of EGFR in breast cancer cells, which may provide new ideas for breast cancer treatment.

scholarly journals KISS1R Induces Invasiveness of Estrogen Receptor-Negative Human Mammary Epithelial and Breast Cancer Cells

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 1999-2014 ◽  
Author(s):  
Donna Cvetković ◽  
Magdalena Dragan ◽  
Sean J. Leith ◽  
Zuhaib M. Mir ◽  
Hon S. Leong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mammary Epithelial ◽  
Metastasis Suppressor ◽  
Dependent Manner ◽  
Egfr Transactivation ◽  
Exogenous Expression ◽  
Mcf10a Cells

Abstract Kisspeptins (KPs), peptide products of the KISS1 metastasis-suppressor gene, are endogenous ligands for a G protein-coupled receptor (KISS1R). KISS1 acts as a metastasis suppressor in numerous human cancers. However, recent studies have demonstrated that an increase in KISS1 and KISS1R expression in patient breast tumors correlates with higher tumor grade and metastatic potential. We have shown that KP-10 stimulates invasion of estrogen receptor α (ERα)-negative MDA-MB-231 breast cancer cells via transactivation of the epidermal growth factor receptor (EGFR). Here, we report that either KP-10 treatment of ERα-negative nonmalignant mammary epithelial MCF10A cells or expression of KISS1R in MCF10A cells induced a mesenchymal phenotype and stimulated invasiveness. Similarly, exogenous expression of KISS1R in ERα-negative SKBR3 breast cancer cells was sufficient to trigger invasion and induced extravasation in vivo. In contrast, KP-10 failed to transactivate EGFR or stimulate invasiveness in the ERα-positive MCF7 and T47D breast cancer cells. This suggested that ERα negatively regulates KISS1R-dependent breast cancer cell migration, invasion, and EGFR transactivation. In support of this, we found that these KP-10-induced effects were ablated upon exogenous expression of ERα in the MDA-MB-231 cells, by down-regulating KISS1R expression. Lastly, we have identified IQGAP1, an actin cytoskeletal binding protein as a novel binding partner of KISS1R, and have shown that KISS1R regulates EGFR transactivation in breast cancer cells in an IQGAP1-dependent manner. Overall, our data strongly suggest that the ERα status of mammary cells dictates whether KISS1R may be a novel clinical target for treating breast cancer metastasis.

scholarly journals Activated Src increases adhesion, survival and alpha2-integrin expression in human breast cancer cells

2004 ◽  
Vol 378 (2) ◽  
pp. 559-567 ◽  
Author(s):  
Hee Boong PARK ◽  
Vita GOLUBOVSKAYA ◽  
Lihui XU ◽  
Xihui YANG ◽  
Jin Woo LEE ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
Focal Adhesions ◽  
Cellular Adhesion ◽  
Dominant Negative ◽  
Breast Cancer Cell Lines ◽  
Src Tyrosine Kinase ◽  
Enhanced Expression

Focal adhesion kinase (FAK) is an intracellular kinase that localizes to focal adhesions. FAK is overexpressed in human tumours, and FAK regulates both cellular adhesion and anti-apoptotic survival signalling. Disruption of FAK function by overexpression of the FAK C-terminal domain [FAK-CD, analogous to the FRNK (FAK-related non-kinase) protein] leads to loss of adhesion and apoptosis in tumour cells. We have shown that overexpression of an activated form of the Src tyrosine kinase suppressed the loss of adhesion induced by dominant-negative; adenoviral FAK-CD and decreased the apoptotic response in BT474 and MCF-7 breast cancer cell lines. This adhesion-dependent apoptosis was increased by the Src-family kinase inhibitor PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine}. We have also shown that expression of activated Src in breast cancer cells increased the expression of α2-integrin and that overexpression of α2-integrin suppressed FAK-CD-mediated loss of adhesion. Our results suggest a model in which Src regulates adhesion and survival through enhanced expression of the α2-integrin. This provides a mechanism through which Src promotes cellular adhesion and alters the adhesive function of FAK.

scholarly journals Whole-genome screen identifies diverse pathways that negatively regulate ciliogenesis

2020 ◽  
pp. mbc.E20-02-0111
Author(s):  
Marion Failler ◽  
Ariadna Giro-Perafita ◽  
Mikito Owa ◽  
Shalini Srivastava ◽  
Chi Yun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cellular Adhesion ◽  
Reciprocal Relationship ◽  
Whole Genome ◽  
Cell Growth And Migration ◽  
Basal Breast Cancer ◽  
Mechanistic Basis

We performed a high-throughput whole-genome RNAi screen to identify novel inhibitors of ciliogenesis in normal and basal breast cancer cells. Our screen uncovered a previously undisclosed, extensive network of genes linking integrin signaling and cellular adhesion to the extracellular matrix with inhibition of ciliation in both normal and cancer cells. Surprisingly, a cohort of genes encoding extracellular matrix (ECM) proteins was also identified. We characterized several ciliation inhibitory genes and showed that their silencing was accompanied by altered cytoskeletal organization and induction of ciliation, which restricts cell growth and migration in normal and breast cancer cells. Conversely, supplying an integrin ligand, vitronectin, to the ECM rescued the enhanced ciliation observed upon silencing this gene. Aberrant ciliation could also be suppressed through hyper-activation of the YAP/TAZ pathway, indicating a potential mechanistic basis for our findings. Our findings suggest an unanticipated reciprocal relationship between ciliation and cellular adhesion to the extracellular matrix and provide a resource that could vastly expand our understanding of controls involving “outside-in” and “inside-out” signaling that restrain cilium assembly.

scholarly journals Thrombospondin-1 (TSP-1) Stimulates Expression of Integrinα6 in Human Breast Carcinoma Cells: A Downstream Modulator of TSP-1-Induced Cellular Adhesion

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Anitha S. John ◽  
Vicki L. Rothman ◽  
George P. Tuszynski
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Human Keratinocytes ◽  
Cellular Adhesion ◽  
Immunohistochemical Localization ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Thrombospondin 1

Thrombospondin-1 (TSP-1) is involved in a variety of different cellular processes including cell adhesion, tumor progression, and angiogenesis. This paper reports the novel finding that TSP-1 upregulates integrinα6 subunit in human keratinocytes and human breast cancer cells resulting in increased cell adhesion and tumor cell invasion. The effect of TSP-1 onα6 subunit expression was examined in human keratinocytes and breast adenocarcinoma cell lines (MDA-MB-231) treated with TSP-1 and in TSP-1 stably transfected breast cancer cells. TSP-1 upregulatedα6 message and protein in these cells as revealed by differential display, Northern and Western blot analysis and immunohistochemical localization studies. The increased expression ofα6 was shown to mediate adhesion and invasion of these cells to laminin, a major component of the basement membrane and extracellular matrix (ECM). These data suggest that TSP-1 plays an integral role in the attachment of cells to the ECM facilitating cell motility and angiogenesis.

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