2. Academic Validation
  3. PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR

PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR

  • Biochim Biophys Acta Mol Basis Dis. 2024 Oct;1870(7):167440. doi: 10.1016/j.bbadis.2024.167440.
Anqi Guan 1,  Ziyu Dai 2,  Chen Jiang 2,  Jingyi Sun 2,  Baishuang Yang 3,  Bin Xie 2,  Qiong Chen 4
Affiliations

Affiliations

  • 1 Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 2 Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 3 Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
  • 4 Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, China; Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: qiongch@csu.edu.cn.
PMID: 39059592 DOI: 10.1016/j.bbadis.2024.167440
Abstract

Cancer Stem Cells (CSCs) are responsible for tumor chemoresistance, and the Aryl Hydrocarbon Receptor (AHR) is indispensable for maintaining CSC characteristics. Here, we aimed to investigate how the interaction between Progesterone Receptor membrane component 1 (PGRMC1) and AHR contributes to the maintenance of CSC phenotypes in non-small cell lung Cancer (NSCLC). Clinical data and tissue microarray analyses indicated that patients with elevated PGRMC1 expression had poorer prognoses. Moreover, PGRMC1 overexpression enhanced CSC phenotypes and chemotherapy resistance in vitro and in vivo by modulating AHR ubiquitination. We then determined the specific interaction sites between PGRMC1 and AHR. Mass spectrometry screening identified tripartite motif containing 56 (TRIM56) as the E3 Ligase targeting AHR. Notably, PGRMC1 overexpression inhibited the interaction between TRIM56 and AHR. Overall, our study revealed a regulatory mechanism that involves PGRMC1, AHR, and TRIM56, providing insights for developing CSC-targeting strategies in NSCLC treatment.

Keywords

AHR; NSCLC; PGRMC1; Stemness; TRIM56; Ubiquitylation.

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