TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathwayopen access
- Authors
- Oh, Se Jin; Lim, Ji Yeon; Son, Min Kyu; Ahn, Jun Hyeok; Song, Kwon-Ho; Lee, Hyo-Jung; Kim, Suyeon; Cho, Eun Ho; Chung, Joon-Yong; Cho, Hanbyoul; Kim, Hyosun; Kim, Jae-Hoon; Park, Jooyoung; Choi, Jungmin; Hwang, Sun Wook; Kim, Tae Woo
- Issue Date
- May-2023
- Publisher
- Nature Publishing Group
- Citation
- Nature Communications, v.14, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- Nature Communications
- Volume
- 14
- Number
- 1
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63489
- DOI
- 10.1038/s41467-023-38318-7
- ISSN
- 2041-1723
2041-1723
- Abstract
- Cisplatin resistance along with chemotherapy-induced neuropathic pain is an important cause of treatment failure for many cancer types and represents an unmet clinical need. Therefore, future studies should provide evidence regarding the mechanisms of potential targets that can overcome the resistance as well as alleviate pain. Here, we show that the emergence of cisplatin resistance is highly associated with EGFR hyperactivation, and that EGFR hyperactivation is arisen by a transcriptional increase in the pain-generating channel, TRPV1, via NANOG. Furthermore, TRPV1 promotes autophagy-mediated EGF secretion via Ca2+ influx, which activates the EGFR-AKT signaling and, consequentially, the acquisition of cisplatin resistance. Importantly, TRPV1 inhibition renders tumors susceptible to cisplatin. Thus, our findings indicate a link among cisplatin resistance, EGFR hyperactivation, and TRPV1-mediated autophagic secretion, and implicate that TRPV1 could be a crucial drug target that could not only overcome cisplatin resistance but also alleviate pain in NANOG+ cisplatin-resistant cancer.
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- Appears in
Collections - 3. Graduate School > Biomedical Research Center > 1. Journal Articles
- 4. Research institute > Translational Research Institute for Incurable Diseases > 1. Journal Articles
- 4. Research institute > Neuroscience Research Institute > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
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