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Research Paper|Volume 15, Issue 13|pp 6380—6399

DSC2 suppresses the growth of gastric cancer through the inhibition of nuclear translocation of γ-catenin and PTEN/PI3K/AKT signaling pathway

Chao Sun1, Kun Wen4, Bin Zhang1, Yan Dong1, Chen Chen1, Shi-Yong Neo5, Bing Leng2, Tian-Tian Gao2, Jing Wu3
  • 1Department of Pharmacy, The Second Hospital of Shandong University, Jinan 250033, China
  • 2Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
  • 3Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
  • 4Department of Critical Care Medicine, The Second Hospital of Shandong University, Jinan 250033, China
  • 5Singapore Immunology Network, Singapore 138648, Singapore
Received: March 14, 2023Accepted: June 15, 2023Published: July 8, 2023
https://doi.org/10.18632/aging.204858

Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Globally, gastric cancer (GC) is still a major leading cause of cancer-associated deaths. Downregulated desmocollin2 (DSC2) is considered to be closely related to tumor progression. However, the underlying mechanisms of DSC2 in GC progression require further exploration.

Method: We initially constructed different GC cells based on DSC2 contents, established the mouse tumor xenografts, and subsequently performed clonal formation, MTT, Caspase-3 activity, and sperm DNA fragmentation assays to detect the functions of DSC2 in GC growth. Subsequently, we performed western blot, Co-IP, and immunofluorescence assays to investigate the underlying mechanisms through pretreatment with PI3K inhibitor, LY294002, and its activator, recombinant human insulin-like growth factor I (IGF1).

Result: DSC2 could significantly inhibit the viability of GC cells at both in vitro and in vivo levels. The underlying mechanism may be that DSC2 binds the γ-catenin to decrease its nuclear level, thereby downregulating the anti-apoptotic factor BCL-2 expression and upregulating the pro-apoptotic factor P53 expression, which adjusts the PTEN/PI3K/AKT signaling pathway to promote the cancer cell apoptosis.

Conclusions: Our finding suggests that DSC2 might be a potential therapeutic target for the treatment of cancers, most especially GC.