BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells through PI3K/AKT/mTOR and STAT3 pathways

Oncotarget
Yuanyuan LiWen-Ting Yang

Abstract

Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be involved in cell proliferation, differentiation, apoptosis, migration and invasion in several types of tumors, but its role in cervical carcinoma remains poorly understood. In this study, we showed that BMX expression exhibits a gradually increasing trend from normal cervical tissue to cervical cancer in situ and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell proliferation was significantly decreased. Knockdown of BMX in HeLa and SiHa cervical cancer cell lines using two different silencing technologies, TALEN and shRNA, inhibited cell growth in vitro and suppressed xenograft tumor formation in vivo, whereas overexpression of BMX in the cell line C-33A significantly increased cell proliferation. Furthermore, a mechanism study showed that silencing BMX blocked cell cycle transit from G0/G1 to S or G2/M phase, and knockdown of BMX inhibited the expression of p-AKT and p-STAT3. These results suggested that BMX can promote cell proliferation through PI3K/AKT/mTOR and STAT3 signaling pathways in cervical cancer cells.

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Citations

Feb 18, 2020·British Journal of Haematology·Stephanie JordaensBarbara-Ann Guinn
Jun 14, 2020·International Journal of Molecular Sciences·Julian Matthias MetzlerPatrick Imesch
Jan 26, 2018·Journal of Receptor and Signal Transduction Research·Pingping DongLin Tian
Jan 11, 2019·Cancer Chemotherapy and Pharmacology·Xing ChenRuoran Mi
Nov 16, 2019·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Kai LiJing-Wei Zhang

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Methods Mentioned

BETA
flow cytometry
Xenografts
X-ray
PCR
transfection
fluorescence-activated cell sorting
genotyping
xenograft

Software Mentioned

FlowJo
GraphPad Prism
GLOBOCAN
Quantity One

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