TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma.

Abstract

Objective: Tetratricopeptide repeat (TRP)-mediated cofactor proteins are involved in a wide range of cancers. TTC36 is little studied member of TRP subfamily. This study aimed to investigate the role of TTC36 in human gastric carcinoma (GC) and explore the potential underlying mechanisms. Methods: The analysis of TTC36 differential expression in GC was conducted using data from TCGA and a human tissue microarray. And effects of TTC36 expression on the prognosis of patients with gastric carcinoma were analyzed using the data from the GEO database. Lentivirus was transfected into the cell lines of AGS and BGC823 to construct overexpression and knocked down TTC36 cell model respectively. The effect of TTC36 expression on the growth, apoptosis and cell cycle of cells was explored in vitro. Downstream molecules were detected by western blotting. GSEA predicted signal pathway and related proteins were then detected. Results: TTC36 expression in human GC tissues was found significantly lower than that in adjacent normal tissues and closely related to clinical prognosis. The overexpression of TTC36 notably inhibited tumor progression, cell cycle G1/S transfer and increased apoptosis in AGS cells. Conversely, the opposite effects were observed when TTC36 was suppressed in BGC823 cells. The expression of cleaved caspase3, Survivin, cyclin D1 and c-Myc were consistent with the phenotype in TTC36 operated GC cell lines. Intriguingly, GSEA analysis predicted Wnt-β-catenin pathway involved in TTC36 induced effects in GC cells, expression of β-catenin and downstream molecules such as TCF4, c-jun and pAKT were found negative related to TTC36 expression in GC cells. Notably, treatment with the Wnt/β-catenin inhibitor XAV939 dramatically attenuated the effects of TTC36 in GC cells. Conclusion: These results signify a critical role for TTC36 as a tumor suppressor in gastric carcinoma via regulating Wnt-β-catenin pathway.

• Authors: Lei Song, Xiaonong Guo, Fei Zhao, Wei Wang, Zhifang Zhao, Long Jin, Chengli Wu, Jibin Yao, Zhongren Ma
• Journal: Journal of Cancer (J Cancer) Vol. 12 Issue 9 Pg. 2598-2609 ( 2021) ISSN: 1837-9664 [Print] Australia
• PMID: 33854620 (Publication Type: Journal Article)
• Copyright: © The author(s).