J Cancer 2021; 12(9):2598-2609. doi:10.7150/jca.47292 This issue Cite

Research Paper

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

Lei Song1,2, Xiaonong Guo1, Fei Zhao1,2, Wei Wang3, Zhifang Zhao2, Long Jin2, Chengli Wu2, Jibin Yao4✉, Zhongren Ma1✉

1. Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, Gansu, China.
2. Department of Medicine, Northwest Minzu University, Lanzhou 730030, Gansu, China.
3. Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, Gansu, China.
4. Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China.

Citation:
Song L, Guo X, Zhao F, Wang W, Zhao Z, Jin L, Wu C, Yao J, Ma Z. TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma. J Cancer 2021; 12(9):2598-2609. doi:10.7150/jca.47292. https://www.jcancer.org/v12p2598.htm
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Abstract

Graphic 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.

Keywords: gastric carcinoma, Hsp70 binding protein 21 (HBP21), beta-catenin, apoptosis, proliferation, xenograft


Citation styles

APA
Song, L., Guo, X., Zhao, F., Wang, W., Zhao, Z., Jin, L., Wu, C., Yao, J., Ma, Z. (2021). TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma. Journal of Cancer, 12(9), 2598-2609. https://doi.org/10.7150/jca.47292.

ACS
Song, L.; Guo, X.; Zhao, F.; Wang, W.; Zhao, Z.; Jin, L.; Wu, C.; Yao, J.; Ma, Z. TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma. J. Cancer 2021, 12 (9), 2598-2609. DOI: 10.7150/jca.47292.

NLM
Song L, Guo X, Zhao F, Wang W, Zhao Z, Jin L, Wu C, Yao J, Ma Z. TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma. J Cancer 2021; 12(9):2598-2609. doi:10.7150/jca.47292. https://www.jcancer.org/v12p2598.htm

CSE
Song L, Guo X, Zhao F, Wang W, Zhao Z, Jin L, Wu C, Yao J, Ma Z. 2021. TTC36 inactivation induce malignant properties via Wnt-β-catenin pathway in gastric carcinoma. J Cancer. 12(9):2598-2609.

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