CCT5 induces epithelial-mesenchymal transition to promote gastric cancer lymph node metastasis by activating the Wnt/β-catenin signalling pathway.

Abstract

BACKGROUND:

Lymph node (LN) metastasis confers gastric cancer (GC) progression, poor survival and cancer-related death. Aberrant activation of Wnt/β-catenin promotes epithelial-mesenchymal transition (EMT) and LN metastasis, whereas the constitutive activation mutation of Wnt/β-catenin is rare in GC, suggesting that the underlying mechanisms enhancing Wnt/β-catenin activation need to be further investigated and understood.

METHODS:

Bioinformatics analyses and immunohistochemistry (IHC) were used to identify and detect LN metastasis-related genes in GC. Cellular functional assays and footpad inoculation mouse model illustrate the biological function of CCT5. Co-immunoprecipitation assays, western blot and qPCR elucidate the interaction between CCT5 and E-cadherin, and the regulation on β-catenin activity.

RESULTS:

CCT5 is upregulated in LN metastatic GCs and correlates with poor prognosis. In vitro assays prove that CCT5 markedly promotes GC cell proliferation, anti-anoikis, invasion and lymphatic tube formation. Moreover, CCT5 enhances xenograft GC growth and popliteal lymph node metastasis in vivo. Furthermore, CCT5 binds the cytoplasmic domain of E-cadherin and abrogates the interaction between E-cadherin and β-catenin, thereby releasing β-catenin to the nucleus and enhancing Wnt/β-catenin signalling activity and EMT.

CONCLUSION:

CCT5 promotes GC progression and LN metastasis by enhancing wnt/β-catenin activation, suggesting a great potential of CCT5 as a biomarker for GC diagnosis and therapy.

• Authors: Yun Li, Chenying Liu, Xin Zhang, Xiaodi Huang, Shujun Liang, Feiyue Xing, Han Tian
• Journal: British journal of cancer (Br J Cancer) Vol. 126 Issue 12 Pg. 1684-1694 (06 2022) ISSN: 1532-1827 [Electronic] England
• PMID: 35194191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• CCT5 protein, human
• CTNNB1 protein, human
• beta Catenin
• Chaperonin Containing TCP-1

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Chaperonin Containing TCP-1 (genetics, metabolism)
• Epithelial-Mesenchymal Transition (genetics)
• Heterografts
• Humans
• Lymphatic Metastasis
• Mice
• Neoplasm Metastasis
• Stomach Neoplasms (genetics, metabolism, pathology)
• Wnt Signaling Pathway
• beta Catenin (genetics, metabolism)