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Archive > Volume 33 Issue 2 > 2026,33(2):174-180. DOI:10.3872/j.issn.1007-385X.2026.02.009 Prev Next
Basic Research
SHCBP1 promotes proliferation, migration, and invasion of colorectal cancer Caco-2 cells by regulating the PI3K/AKT/mTOR signaling pathway
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Abstract:
[Abstract] Objective: To investigate the expression of Shc SH2 domain-binding protein 1 (SHCBP1) in colorectal cancer (CRC) and its regulatory mechanism on Caco-2 cell proliferation, migration, and invasion. Methods: Caco-2 cells were divided into four experimental groups: the Con group (blank control), the sh-NC group (transfection with negative control sh-NC), the sh-SHCBP1 group (transfection with sh-SHCBP1), and the sh-SHCBP1 + 740Y-P group (transfection with sh-SHCBP1 followed by treatment with the PI3K activator 740Y-P at 30 μmol/L for 1 h). Cell proliferation, migration, and invasion were assessed using the CCK-8 assay, woundhealing, and Transwell invasion assay, respectively. Vasculogenic mimicry (VM) formation in Caco-2 cells was examined using a Matrigel-based three-dimensional culture system. The mRNA expression level of SHCBP1 was detected using qRT-PCR, and the protein expression levels of SHCBP1, VM-related markers, and PI3K/AKT/mTOR signaling pathway-related proteins were detected using WB. Results: SHCBP1 was significantly upregulated in CRC tissues and cell lines (P < 0.05). Compared with Con group and sh-NC group, the sh-SHCBP1 group showed significantly reduced mRNA and protein levels of SHCBP1, cell proliferation activity, wound-healing rate, number of invaded cells, and number of formed tubules (all P < 0.05). In addition, the protein expression levels of hypoxia-inducible factor 1α (HIF-1α), ephrin type-A receptor 2 (EPHA2), VEGFA, p-PI3K, p-AKT, and phosphorylated mTOR (pmTOR) were significantly decreased (all P < 0.05). Compared with the sh-SHCBP1 group, the sh-SHCBP1 + 740Y-P group demonstrated significantly increased cell proliferation, wound-healing rate, number of invaded cells, and number of formed VM structures (all P < 0.05), along with significantly elevated protein expression of HIF-1α, EPHA2, VEGFA, p-PI3K, p-AKT, and pmTOR (all P < 0.05). Conclusion: SHCBP1 is highly expressed in CRC cells and promotes the proliferation, migration, and invasion of Caco-2 cells. The underlying mechanism may be associated with activation of the PI3K/AKT/mTOR signaling pathway and subsequent promotion of the VM process.
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