SHP-2-Mediated Upregulation of ZEB1 Is Important for PDGF-B-Induced Cell Proliferation and Metastatic Phenotype in Triple Negative Breast Cancer

Bibliographic Details
Title: SHP-2-Mediated Upregulation of ZEB1 Is Important for PDGF-B-Induced Cell Proliferation and Metastatic Phenotype in Triple Negative Breast Cancer
Authors: Lei Zhang, Chenwei Yuan, Jing Peng, Liheng Zhou, Yiwei Jiang, Yanping Lin, Wenjin Yin, Shuguang Xu, Jun Ma, Jinsong Lu
Source: Frontiers in Oncology, Vol 10 (2020)
Publisher Information: Frontiers Media S.A., 2020.
Publication Year: 2020
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: PDGF-B, SHP-2, ZEB1, TNBC, metastasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: Background: Triple negative breast cancer (TNBC), a fatal malignant tumor, is characterized by a lack of estrogen and progesterone hormone receptors and overexpression of HER2. Due to its characteristics, there are no effective targeted therapies for TNBC. Therefore, it is critical to identify the crucial factors that participate in modulating TNBC progression and explore the underlying molecular mechanism.Methods: CCK-8, bromodeoxyuridine incorporation, western blotting, qPCR, and transwell assays were utilized to evaluate breast cancer cell proliferation, migration, and invasion.Results: Activation of platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR) promoted the proliferation and metastatic phenotype of TNBC cells; however, these effects were attenuated by SHP-2 knockdown. Moreover, PDGF-B promoted the expression of zinc finger E-box binding homeobox 1 (ZEB1) by downregulating the expression of miR-200. Furthermore, knockdown of ZEB1 mitigated the promoting effects of PDGF-B on cell proliferation and migration. In addition, the regulatory effects of PDGF-B on miR-200 and ZEB1 were mediated through the SHP-2/Akt pathway.Conclusion: Our findings highlight the important roles of PDGF-B/PDGFR and their downstream signaling pathways in regulating cell proliferation and metastatic phenotype in TNBC. Hence, these molecules may serve as novel therapeutic targets for TNBC in the future.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2234-943X
Relation: https://www.frontiersin.org/article/10.3389/fonc.2020.01230/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2020.01230
Access URL: https://doaj.org/article/bd8b563c43824f84b7857a80b3b6140b
Accession Number: edsdoj.bd8b563c43824f84b7857a80b3b6140b
Database: Directory of Open Access Journals
More Details
ISSN:2234943X
DOI:10.3389/fonc.2020.01230
Published in:Frontiers in Oncology
Language:English