The RhoA dependent anti-metastatic function of RKIP in breast cancer
| Autor: | Alexandria LaSalla, Vu N. Bach, Julius N. De Castro, Hussain N. Odeh, Christopher Figy, Rafael Garcia-Mata, Clariza Borile, Miranda Yeung, Gardiyawasam Kalpana, Jingwei Feng, Claire Tipton, Kam C. Yeung |
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| Rok vydání: | 2021 |
| Předmět: |
Cell biology
RHOA Molecular biology Science Apoptosis Breast Neoplasms Phosphatidylethanolamine Binding Protein Biochemistry CCL5 Article Metastasis Mice medicine Genetics Biomarkers Tumor Tumor Cells Cultured Animals Humans Cancer Cell Proliferation Multidisciplinary biology Kinase Chemistry Inhibitor protein Actin cytoskeleton medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Cancer cell biology.protein Cancer research Medicine Female rhoA GTP-Binding Protein Function (biology) |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Raf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression. |
| Databáze: | OpenAIRE |
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