BMP4 promotes hepatocellular carcinoma proliferation by autophagy activation through JNK1-mediated Bcl-2 phosphorylation

Journal of Experimental & Clinical Cancer Research : CR
Ganlu DengHong Shen

Abstract

Autophagy is a conserved catabolic process with complicated roles in tumor development. Bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF-β) family of regulatory proteins, plays a crucial role in human malignancies. However, whether BMP4 contributes to the regulation of autophagy in hepatocellular carcinoma (HCC) progression remains elusive. Functional analysis of BMP4 on HCC proliferation and autophagy was performed both in vitro and in vivo in HepG2 and HCCLM3 cells. Autophagic activity was estimated by Western blot for autophagic marker proteins and by transmission electron microscopy (TEM). Transfection of mRFP-GFP-LC3 adenovirus was applied to observe autophagic flux and high content screening was used for quantification. The signaling pathway of BMP4-regulated HCC proliferation and autophagy was investigated by Western blot. BMP4 treatment promoted HCC cells proliferation and induced autophagy. The in vivo xenograft model supported that BMP4 overexpression promoted the growth of HCC cells and autophagy induction while BMP4 knockdown exerted the opposite effect. 3-MA pre-treatment or knockdown of Beclin-1 (BECN1) blocked HCC autophagy by decreasing the expression of LC3-II and subsequentl...Continue Reading

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Citations

Nov 7, 2019·Cell Communication and Signaling : CCS·Ulrike NeckmannToril Holien
May 15, 2019·Cancers·Jürgen Eberle
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jia-Qi ShengPei-Yuan Li
Feb 27, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Y HuL Xiao
Mar 14, 2021·Cell Death & Disease·Yafei WuQin Li
May 10, 2021·Reproductive Sciences·Dongyong YangYanxiang Cheng

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Methods Mentioned

BETA
PCR
transfection
xenograft
transmission electron microscopy

Software Mentioned

Image lab
Columbus
Elmer Columbus
GraphPad Prism
Perkin

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