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PD-L1/PD-L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK

Yihui Cao1, Weiye Liang2, Lian Fang2

  • 1School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.

Clinical and Experimental Pharmacology & Physiology
|September 1, 2022
PubMed

Insights

Programmed death ligand 1 (PD-L1) promotes colorectal cancer (CRC) progression by enhancing cell migration and invasion. Understanding PD-L1's role in CRC offers new avenues for effective immunotherapy treatments.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Programmed death ligand 1 (PD-L1) is a known immune checkpoint crucial for anti-tumour immunotherapy via PD-1/PD-L1 pathways.
  • The specific biological functions and expression patterns of PD-L1 in colorectal cancer (CRC) remain incompletely understood.
  • Previous research indicated PD-L1 binding can induce cell detachment, but the underlying molecular mechanisms require clarification.

Purpose of the Study:

  • To elucidate the detailed molecular mechanisms of PD-L1 binding and signal transduction in colorectal cancer.
  • To investigate the expression profile and functional role of PD-L1 in CRC progression.
  • To explore PD-L1's potential as a therapeutic target in CRC immunotherapy.

Main Methods:

  • Quantitative analysis of PD-L1 expression in CRC versus normal tissues.
  • In vitro studies using CRC cell lines with ectopic PD-L1 expression and PD-L1 silencing.
  • Investigation of signalling pathways, including ERK, and protein-protein interactions, specifically with KRAS.

Main Results:

  • PD-L1 expression is significantly upregulated in colorectal cancer tissues compared to normal tissues.
  • Overexpression of PD-L1 in CRC cells reduces adhesion and increases migration, while PD-L1 silencing inhibits invasion and proliferation.
  • PD-L1 promotes epithelial-mesenchymal transition (EMT) via the ERK pathway and interacts with the KRAS 1-86 aa fragment for signal transduction.

Conclusions:

  • PD-L1 plays a significant role in promoting colorectal cancer progression through enhanced cell migration, invasion, and EMT.
  • The interaction of PD-L1 with KRAS and its activation of the ERK pathway are key mechanisms driving these effects.
  • These findings provide a novel theoretical foundation for enhancing the efficacy of anti-PD-L1 antibody immunotherapy in CRC treatment.
Keywords:
ERKKRASPD-L1cell adhesioncolorectal cancer (CRC)migration

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