Gut Liver.  2023 May;17(3):412-429. 10.5009/gnl210494.

TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway

• Zhu X
• Jiang X
• Zhang Q
• Huang H
• Shi X
• Hou D
• Xing C

• KMID: 2542343
• DOI: http://doi.org/10.5009/gnl210494

Abstract

Background/Aims
This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC).
Methods
We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo.
Results
TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage.
Conclusions
TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.

Keyword

TCN1; Proliferation; Invasion; Colorectal neoplasms; ITGB4 pathway