ArticleCellular and molecular life sciences : CMLS2023
HIF-1α-activated TMEM237 promotes hepatocellular carcinoma progression via the NPHP1/Pyk2/ERK pathway.
Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 19 citations in OpenAlex.
- Inhibiting Pyk2/Src expression by miR-23b-3p suppressed liver cancer stem cell function and hepatic carcinoma progression.Cancer cell international · 2025Article
- The emerging role of transmembrane proteins in tumorigenesis and therapy.Translational cancer research · 2025Review
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- OTUD5 promotes the growth of hepatocellular carcinoma by deubiquitinating and stabilizing SLC38A1.Biology direct · 2024Article
- Early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1/2 pathway and epithelial-mesenchymal transition during wound healing.Burns & trauma · 2024Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundHypoxia-inducible factors (HIFs) are the most essential endogenous transcription factors in the hypoxic microenvironment and regulate multiple genes involved in the proliferation, migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells. However, the regulatory mechanism of HIFs in driving HCC progression remains poorly understood.
methodsGain- and loss-of-function experiments were carried out to investigate the role of TMEM237 in vitro and in vivo. The molecular mechanisms involved in HIF-1α-induced TMEM237 expression and TMEM237-mediated enhancement of HCC progression were confirmed by luciferase reporter, ChIP, IP-MS and Co-IP assays.
resultsTMEM237 was identified as a novel hypoxia-responsive gene in HCC. HIF-1α directly bound to the promoter of TMEM237 to transactivate its expression. The overexpression of TMEM237 was frequently detected in HCC and associated with poor clinical outcomes in patients. TMEM237 facilitated the proliferation, migration, invasion, and EMT of HCC cells and promoted tumor growth and metastasis in mice. TMEM237 interacted with NPHP1 and strengthened the interaction between NPHP1 and Pyk2 to trigger the phosphorylation of Pyk2 and ERK1/2, thereby contributing to HCC progression. The TMEM237/NPHP1 axis mediates hypoxia-induced activation of the Pyk2/ERK1/2 pathway in HCC cells.
conclusionsOur study demonstrated that HIF-1α-activated TMEM237 interacted with NPHP1 to activate the Pyk2/ERK pathway, thereby promoting HCC progression.
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