ArticleJournal of experimental & clinical cancer research : CR2018
BMP4 promotes hepatocellular carcinoma proliferation by autophagy activation through JNK1-mediated Bcl-2 phosphorylation.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Icariin mediates autophagy and apoptosis of hepatocellular carcinoma cells induced by the β-catenin signaling pathway through lncRNA LOXL1-AS1.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Review
- Exosome-Delivered circFOXP1 Upregulates Autophagy and Promotes Hepatocellular Carcinoma Progression Through Its Encoded p196 Protein Targeting the KHDRBS3/ULK1 Axis.International journal of nanomedicine · 2025Article
- ARF alters PAF1 complex integrity to selectively repress oncogenic transcription programs upon p53 loss.Molecular cell · 2024Article
- Cervical Cancer Cells Use the CD95 and IL-2 Pathways to Promote Their Proliferation and Survival.Biomolecules · 2024Article
- Transcriptional and post-transcriptional regulation of CARMN and its anti-tumor function in cervical cancer through autophagic flux blockade and MAPK cascade inhibition.Journal of experimental & clinical cancer research : CR · 2024Article
- Autophagy accompanying the developmental process of male germline stem cells.Cell and tissue research · 2024Review
- Bone Morphogenetic Protein Signaling Agonist SB4 (BMPSB4) Inhibits Corticotroph Pituitary Neuroendocrine Tumors by Activation of Autophagy via a BMP4/SMADs-Dependent Pathway.ACS pharmacology & translational science · 2024Article
- Advances in the study of autophagy in breast cancer.Breast cancer (Tokyo, Japan) · 2024Review
- Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions.International journal of molecular sciences · 2023Review
- BMP4 upregulates glycogen synthesis through the SMAD/SLC2A1 (GLUT1) signaling axis in hepatocellular carcinoma (HCC) cells.Cancer & metabolism · 2023Article
- BMP signaling inhibition overcomes chemoresistance of prostate cancer.American journal of cancer research · 2023Article
- Bone morphogenetic protein 4 inhibits pulmonary fibrosis by modulating cellular senescence and mitophagy in lung fibroblasts.The European respiratory journal · 2022Article
- ULK1 Signaling in the Liver: Autophagy Dependent and Independent Actions.Frontiers in cell and developmental biology · 2022Review
- Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years.Frontiers in cell and developmental biology · 2022Review
- KLK6 Functions as an Oncogene and Unfavorable Prognostic Factor in Bladder Urothelial Carcinoma.Disease markers · 2022Article
- FGF10 ameliorates lipopolysaccharide-induced acute lung injury in miceFrontiers in pharmacology · 2022Article
- The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases.Reproductive sciences (Thousand Oaks, Calif.) · 2021Review
- Expression of bone morphogenetic protein 10 in cases with endometrial carcinoma and its clinical significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Autophagy, an accomplice or antagonist of drug resistance in HCC?Cell death & disease · 2021Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAutophagy 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.
methodsFunctional 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.
resultsBMP4 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 subsequently attenuated BMP4-induced autophagy and cells proliferation enhanced by BMP4 in vitro and in vivo. Mechanistic study revealed that the induction of autophagy by BMP4 was mediated through activating the JNK1/Bcl2 pathway. Furthermore, the JNK1 inhibitor and knockdown of JNK1 could attenuate autophagy induced by BMP4 and eliminated BMP4-promoted HCC cells growth.
conclusionsBMP4 promoted HCC proliferation by autophagy activation through JNK1/Bcl-2 signaling.
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