TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway

Se Jin Oh, Ji Yeon Lim, Min Kyu Son, Jun Hyeok Ahn, Kwon-Ho Song, Hyo-Jung Lee, Suyeon Kim, Eun Ho Cho, Joon-Yong Chung, Hanbyoul Cho, Hyosun Kim, Jae-Hoon Kim, Jooyoung Park, Jungmin Choi, Sun Wook Hwang and Tae Woo Kim ()
Additional contact information
Se Jin Oh: Korea University College of Medicine
Ji Yeon Lim: Korea University College of Medicine
Min Kyu Son: Korea University College of Medicine
Jun Hyeok Ahn: Korea University College of Medicine
Kwon-Ho Song: Daegu Catholic University School of Medicine
Hyo-Jung Lee: Korea University College of Medicine
Suyeon Kim: Korea University College of Medicine
Eun Ho Cho: Korea University College of Medicine
Joon-Yong Chung: National Cancer Institute, National Institutes of Health
Hanbyoul Cho: Gangnam Severance Hospital, Yonsei University College of Medicine
Hyosun Kim: Gangnam Severance Hospital, Yonsei University College of Medicine
Jae-Hoon Kim: Gangnam Severance Hospital, Yonsei University College of Medicine
Jooyoung Park: Korea University College of Medicine
Jungmin Choi: Korea University College of Medicine
Sun Wook Hwang: Korea University College of Medicine
Tae Woo Kim: Korea University College of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38318-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38318-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38318-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().