Targeting Nuclear Receptor Coactivator SRC-1 Prevents Colorectal Cancer Immune Escape by Reducing Transcription and Protein Stability of PD-L1

Authors

Yilin Hong
Qiang Chen
Zinan Wang
Yong Zhang
Bei Li
Hanshi Guo
Chuanzhong Huang
Xu Kong
Pingli Mo
Nengming Xiao
Jianming Xu
Yunbin Ye
Chundong Yu

Publication Date

9-1-2024

Journal

Advanced Science

DOI

10.1002/advs.202310037

PMID

38953362

PMCID

PMC11434141

PubMedCentral® Posted Date

7-2-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Colorectal Neoplasms, Animals, Mice, B7-H1 Antigen, Humans, Nuclear Receptor Coactivator 1, Tumor Escape, Disease Models, Animal, Protein Stability, Cell Line, Tumor, Mice, Inbred C57BL

Abstract

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8

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