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Transient receptor potential vanilloid 1 promotes EGFR ubiquitination and modulates EGFR/MAPK signalling in pancreatic cancer cells
Author(s) -
Huang Jin,
Liu Jingxue,
Qiu Lei
Publication year - 2020
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3483
Subject(s) - trpv1 , pancreatic cancer , epidermal growth factor receptor , cancer research , transient receptor potential channel , chemistry , mapk/erk pathway , egfr inhibitors , kras , cell growth , signal transduction , cancer , receptor , medicine , colorectal cancer , biochemistry
Transient receptor potential vanilloid‐1 (TRPV1) was first identified in sensory neurons, where it was suggested as a therapeutic target for pain relief. Here, we show that TRPV1 is expressed in the pancreatic cancer cell line, PANC‐1; that epidermal growth factor receptor (EGFR) expression is downregulated by overexpression or agonist‐induced activation of TRPV1; and conversely, that EGFR expression is increased after silencing TRPV1. Furthermore, TRPV1 overexpression inhibits cell proliferation and significantly reduces the mRNA levels of two oncogenes, KRAS and AKT2 . More importantly, TRPV1 downregulates EGFR levels by inducing EGFR ubiquitination and degradation, which modulate EGFR/MAPK signalling in pancreatic cancer cells. These results illustrate the regulation and mechanism of TRPV1 on EGFR in pancreatic cancer cells and may provide new ideas for the design of novel antitumor drugs targeting EGFR. Significance of the study We investigated the effect and mechanism of TRPV1 on EGFR‐mediated proliferation and transformation of pancreatic cancer cells, with the aim of providing new ideas and experimental evidence for the application of strategies that promote EGFR degradation to treat pancreatic cancer.