Epithelial to mesenchymal transition regulates surface pd-l1 via cmtm6 and cmtm7 induction in breast cancer

Malina Xiao, Meriem Hasmim, Audrey Lequeux, Kris Van Moer, Tuan Zea Tan, Christine Gilles, Brett G. Hollier, Jean Paul Thiery, Guy Berchem, Bassam Janji*, Muhammad Zaeem Noman

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7Mes cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7Mes cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7Mes cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7Mes cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. This study highlights the importance of CMTM6 and CMTM7 in EMT-induced PD-L1 and suggests that EMT, CMTM6 or CMTM7 modulators can be combined with anti-PD-L1 in patients with highly aggressive breast cancer.

Original languageEnglish
Article number1165
Pages (from-to)1-12
Number of pages12
JournalCancers
Volume13
Issue number5
DOIs
Publication statusPublished - 9 Mar 2021

Keywords

  • Breast cancer
  • CMTM family
  • Epithelial to mesenchymal transition
  • Immune checkpoints
  • Snail1

Fingerprint

Dive into the research topics of 'Epithelial to mesenchymal transition regulates surface pd-l1 via cmtm6 and cmtm7 induction in breast cancer'. Together they form a unique fingerprint.

Cite this