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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1562976
Tricellulin facilitates colorectal cancer metastasis through activation of the TGFβ/SMAD2/3 signaling pathway
Provisionally accepted- Department of Gastroenterology, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
Tricellulin belongs to the TAMP family of proteins and is primarily localized at the tricellular tight junctions. While its role in the progression of cancer has been reported, its importance in the progression of colorectal cancer (CRC) remains unclear. This study aimed to determine the function and mechanism of tricellulin in CRC progression. The proteins expression in cells and/or tissues was determined by Western blot, immunohistochemistry staining, and/or RT-qPCR analyses. The biological functions of tricellulin were investigated through in vitro assays (CCK-8, Transwell migration, and colony formation assays) and in vivo xenograft models.Tricellulin was significantly upregulated in CRC tissues compared to adjacent normal tissues. The expression of tricellulin was correlated with poor prognosis in patients with CRC. In vitro assays showed that tricellulin enhanced CRC cell proliferation, migration, and invasion. Mechanistically, tricellulin activated the TGFβ1/SMAD2/3 pathway, while TGFβ1 reciprocally controlled the expression of tricellulin. Also, tricellulin promotes CRC cell migration/invasion through EMT. In vivo models confirmed that the overexpression of tricellulin facilitated tumor growth and activated the TGFβ1/SMAD2/3 pathway in CRC. We have revealed a novel mechanism by which tricellulin forms a positive feedback loop to promote the growth and metastasis of CRC. This mechanism provides novel insights into CRC progression and suggests potential therapeutic targets.
Keywords: colorectal cancer, tricellulin, TGFβ/Smad signaling, metastasis, Epithelial-Mesenchymal Transition
Received: 18 Jan 2025; Accepted: 17 Mar 2025.
Copyright: © 2025 Yang, Cheng, Qin, Pan, Tan, Feng, Zhang and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jinxiu Zhang, Department of Gastroenterology, Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Zhuang Region, China
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