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Published on: June 12, 2021
TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway
Xinqiang Zhu1,2, Xuetong Jiang2, Qinglin Zhang3
1Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
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-of-function 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.
Insights
TCN1 promotes colorectal cancer (CRC) growth and metastasis by interacting with integrin subunit β4 (ITGB4), highlighting TCN1 as a potential therapeutic target in CRC. This study reveals TCN1
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) remains a significant global health challenge.
- Understanding the molecular mechanisms driving CRC progression is crucial for developing effective treatments.
Purpose of the Study:
- Investigate the biological function of TCN1 in colorectal cancer.
- Elucidate the regulatory mechanisms underlying TCN1's role in CRC.
Main Methods:
- Utilized gain-of-function and loss-of-function analyses in CRC cell lines (HCT116, SW480).
- Performed in vivo studies including mouse xenotransplantation, tumor xenograft, and colonization assays.
- Conducted molecular mechanism analyses to identify protein interactions and signaling pathways.
Main Results:
- TCN1 knockdown inhibited CRC cell proliferation and invasion while promoting apoptosis.
- TCN1 overexpression demonstrated opposing effects on CRC cell behavior.
- TCN1 was found to interact with integrin subunit β4 (ITGB4), positively regulating its expression and stability.
- TCN1 knockdown led to ITGB4 degradation and cytoskeletal damage via the ITGB4/plectin complex.
Conclusions:
- TCN1 plays an oncogenic role in colorectal cancer.
- TCN1 regulates CRC progression through the ITGB4 signaling pathway.
- TCN1 represents a potential therapeutic target for colorectal cancer treatment.
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