AUTHOR=Zhang Lei , Yuan Chenwei , Peng Jing , Zhou Liheng , Jiang Yiwei , Lin Yanping , Yin Wenjin , Xu Shuguang , Ma Jun , Lu Jinsong 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01230

DOI=10.3389/fonc.2020.01230

ISSN=2234-943X

ABSTRACT=Background: Triple negative breast cancer (TNBC), a fatal malignant tumour, is characterized by lack of oestrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to its characteristics, there is no effective molecular therapeutic target. Therefore, it is critical to find the crucial factors that participated in modulating the progression of TNBC and explore the corresponding molecular mechanism. 
Methods: A CCK-8 assay, BrdU incorporation, Western blot, qPCR and Transwell assay were utilized in our study to observe breast cancer cell proliferation, migration and invasion.
Results: In the present study, the data showed that activation of PDGF-B/PDGF receptor (PDGFR) promoted cell proliferation and cell metastasis in TNBC cells, which were attenuated by the knockdown of SHP-2. Moreover, PDGF-B promoted the expression of ZEB1 via downregulating the expression of miR-200. Knockdown of ZEB1 mitigated the promotive effects of PDGF-B on cell proliferation and migration. We also found that the regulatory effects of PDGF-B on miR-200 and ZEB1 were mediated by the SHP-2/Akt pathway. 
Conclusion: These results indicated the important roles of PDGF-B/PDGFR and its downstream signal transduction pathway in regulating cell proliferation and metastasis in TNBC, which may be considered new potential targets for the treatment of TNBC in the future.