A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis

A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis

Bibliographic Details
Main Author: Kalpana, Gardiyawasam
Language:English
Published: University of Toledo Health Science Campus / OhioLINK 2019
Subjects:
Biomedical Research
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=mco1564782498788212
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-mco15647824987882122021-08-03T07:12:14Z A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis Kalpana, Gardiyawasam Biomedical Research Tumor metastasis suppressors impede secondary tumor formation by inhibiting one or more steps of the metastasis cascade without stimulating primary tumor growth. Raf-1 kinase inhibitor protein (RKIP) is a metastasis suppressor that inhibits breast and prostate cancer metastasis. The molecular mechanism through which RKIP executes its anti-metastasis effects is not yet completely defined. The objective of the current study is to understand how RKIP inhibits breast cancer cell invasion and metastasis at the molecular level. Given their primary functions in actin cytoskeleton dynamics and cell movement regulation, Rho GTPases were studied as possible downstream effectors of RKIP. Among all Rho GTPases, RhoA has both pro-metastatic and anti-metastatic cell-context dependent functions. In this study, we demonstrate that the increased anti-metastatic activity of RhoA is one of the causes of RKIP-mediated suppression of breast cancer metastasis. Upon RNAi-mediated RhoA gene knockdown, more tumor cells were detected in the sentinel lymph node and more colonies in the lungs, suggesting that RhoA suppresses breast cancer lymph node and lung metastasis. Further characterizations showed that RhoA suppresses breast cancer lung metastasis partly due to upstream RKIP-dependent signaling and this is mediated through downstream E-cadherin and CCL5. Additionally, RhoA’s effect on tumor chemokine receptor expression and infiltration of SMA+ cells are independent of upstream RKIP signaling and might be mediated by RKIP-independent upstream RhoA regulators. 2019-09-05 English text University of Toledo Health Science Campus / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=mco1564782498788212 http://rave.ohiolink.edu/etdc/view?acc_num=mco1564782498788212 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
spellingShingle Biomedical Research
Kalpana, Gardiyawasam
A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis
author Kalpana, Gardiyawasam
author_facet Kalpana, Gardiyawasam
author_sort Kalpana, Gardiyawasam
title A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis
title_short A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis
title_full A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis
title_fullStr A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis
title_full_unstemmed A Mechanistic Investigation of the Role of RhoA and RKIP in Breast Cancer Invasion and Metastasis
title_sort mechanistic investigation of the role of rhoa and rkip in breast cancer invasion and metastasis
publisher University of Toledo Health Science Campus / OhioLINK
publishDate 2019
url http://rave.ohiolink.edu/etdc/view?acc_num=mco1564782498788212
work_keys_str_mv AT kalpanagardiyawasam amechanisticinvestigationoftheroleofrhoaandrkipinbreastcancerinvasionandmetastasis
AT kalpanagardiyawasam mechanisticinvestigationoftheroleofrhoaandrkipinbreastcancerinvasionandmetastasis
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