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MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer

The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known about the role of MST4 in breast cancer, and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here we report that overexpression o...

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Autores principales: Arora, Ritu, Kim, Jin-Hwan, Getu, Ayechew A., Angajala, Anusha, Chen, Yih-Lin, Wang, Bin, Kahn, Andrea G., Chen, Hong, Reshi, Latif, Lu, Jianrong, Zhang, Wenling, Zhou, Ming, Tan, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777386/
https://www.ncbi.nlm.nih.gov/pubmed/36552828
http://dx.doi.org/10.3390/cells11244057
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author Arora, Ritu
Kim, Jin-Hwan
Getu, Ayechew A.
Angajala, Anusha
Chen, Yih-Lin
Wang, Bin
Kahn, Andrea G.
Chen, Hong
Reshi, Latif
Lu, Jianrong
Zhang, Wenling
Zhou, Ming
Tan, Ming
author_facet Arora, Ritu
Kim, Jin-Hwan
Getu, Ayechew A.
Angajala, Anusha
Chen, Yih-Lin
Wang, Bin
Kahn, Andrea G.
Chen, Hong
Reshi, Latif
Lu, Jianrong
Zhang, Wenling
Zhou, Ming
Tan, Ming
author_sort Arora, Ritu
collection PubMed
description The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known about the role of MST4 in breast cancer, and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here we report that overexpression of MST4 in breast cancer results in enhanced cell growth, migration, and invasion, whereas inhibition of MST4 expression significantly attenuates these properties. Further study shows that MST4 promotes EMT by activating Akt and its downstream signaling molecules such as E-cadherin/N-cadherin, Snail, and Slug. MST4 also activates AKT and its downstream pro-survival pathway. Furthermore, by analyzing breast cancer patient tissue microarray and silicon datasets, we found that MST4 expression is much higher in breast tumor tissue compared to normal tissue, and significantly correlates with cancer stage, lymph node metastasis and a poor overall survival rate (p < 0.05). Taken together, our findings demonstrate the oncogenic potential of MST4 in breast cancer, highlighting its role in cancer cell proliferation, migration/invasion, survival, and EMT, suggesting a possibility that MST4 may serve as a novel therapeutic target for breast cancer.
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spelling pubmed-97773862022-12-23 MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer Arora, Ritu Kim, Jin-Hwan Getu, Ayechew A. Angajala, Anusha Chen, Yih-Lin Wang, Bin Kahn, Andrea G. Chen, Hong Reshi, Latif Lu, Jianrong Zhang, Wenling Zhou, Ming Tan, Ming Cells Article The mammalian STE 20-like protein kinase 4 (MST4) gene is highly expressed in several cancer types, but little is known about the role of MST4 in breast cancer, and the function of MST4 during epithelial-mesenchymal transition (EMT) has not been fully elucidated. Here we report that overexpression of MST4 in breast cancer results in enhanced cell growth, migration, and invasion, whereas inhibition of MST4 expression significantly attenuates these properties. Further study shows that MST4 promotes EMT by activating Akt and its downstream signaling molecules such as E-cadherin/N-cadherin, Snail, and Slug. MST4 also activates AKT and its downstream pro-survival pathway. Furthermore, by analyzing breast cancer patient tissue microarray and silicon datasets, we found that MST4 expression is much higher in breast tumor tissue compared to normal tissue, and significantly correlates with cancer stage, lymph node metastasis and a poor overall survival rate (p < 0.05). Taken together, our findings demonstrate the oncogenic potential of MST4 in breast cancer, highlighting its role in cancer cell proliferation, migration/invasion, survival, and EMT, suggesting a possibility that MST4 may serve as a novel therapeutic target for breast cancer. MDPI 2022-12-15 /pmc/articles/PMC9777386/ /pubmed/36552828 http://dx.doi.org/10.3390/cells11244057 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arora, Ritu
Kim, Jin-Hwan
Getu, Ayechew A.
Angajala, Anusha
Chen, Yih-Lin
Wang, Bin
Kahn, Andrea G.
Chen, Hong
Reshi, Latif
Lu, Jianrong
Zhang, Wenling
Zhou, Ming
Tan, Ming
MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer
title MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer
title_full MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer
title_fullStr MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer
title_full_unstemmed MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer
title_short MST4: A Potential Oncogene and Therapeutic Target in Breast Cancer
title_sort mst4: a potential oncogene and therapeutic target in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777386/
https://www.ncbi.nlm.nih.gov/pubmed/36552828
http://dx.doi.org/10.3390/cells11244057
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