1. Academic Validation
  2. KYA1797K down-regulates PD-L1 in colon cancer stem cells to block immune evasion by suppressing the β-catenin/STT3 signaling pathway

KYA1797K down-regulates PD-L1 in colon cancer stem cells to block immune evasion by suppressing the β-catenin/STT3 signaling pathway

  • Int Immunopharmacol. 2020 Jan;78:106003. doi: 10.1016/j.intimp.2019.106003.
Zhiyan Ruan 1 Minhua Liang 1 Manxiang Lai 1 Ling Shang 1 Xiangliang Deng 2 Xinguo Su 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Guangdong Food and Drug Vocational College, Guangzhou 510520, PR China.
  • 2 School of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: dxl@gdpu.edu.cn.
  • 3 School of Pharmacy, Guangdong Food and Drug Vocational College, Guangzhou 510520, PR China. Electronic address: suxg@gdyzy.edu.cn.
Abstract

Cancer Stem Cells (CSCs) are considered to mediate tumorigenesis, recurrence, and metastasis. KYA1797K, a β-catenin Inhibitor, has been identified for its functionality as a tumor suppressor gene in colorectal Cancer through inhibition of the Wnt/β-catenin signaling pathway. However, it remains uncertain whether KYA1797K attenuates immune evasion of colon CSCs. Hence, this study is designed for evaluating the function of KYA1797K in colon CSCs. The expression of β-catenin and STT3A/B in colon Cancer tissues was initially detected by immunohistochemistry, followed by correlation analyses of the survival rate with the expression of β-catenin and STT3A/B as well as identification of the interaction between β-catenin and STT3A/B. Besides, β-catenin in colon CSCs was knocked down or inhibited by KYA1797K to explore its role in immune evasion and the subsequent underlying mechanism associated with STT3A/B expression and PD-L1 glycosylation. Additionally, the in vivo regulatory effects of β-catenin silencing and KYA1797K were evaluated by assessing tumor formation, detecting CD8 and GZMB expression and CD8+ T cell viability. The results collected displayed that β-catenin and STT3A/B showed high expression in colon Cancer tissues, both of which were correlated with poor survival of colon Cancer patients. β-catenin was found to positively regulate STT3A/B expression. Besides, β-catenin silencing or KYA1797K treatment down-regulated the expression of STT3A/B, inhibited PD-L1 glycosylation and suppressed immune evasion of colon CSCs both in vivo and in vitro. Altogether, KYA1797K inhibits the β-catenin/STT3 signaling pathway to reduce the stability of PD-L1, thus further inhibiting immune evasion and inducing Apoptosis of colon CSCs, which contributes to the development of immunotherapy for colon Cancer.

Keywords

Cancer stem cells; Colon cancer; Immune evasion; KYA1797K; PD-L1; STT3A/B; β-catenin.

Figures
Products