Overexpression of G3BP1 facilitates the progression of colon cancer by activating β‑catenin signaling.

Yuanzhi Li, Jundong Wang, Sen Zhong, Jun Li, Weiliang Du

Molecular medicine reports 2020 Nov

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Ras‑GTPase‑activating protein SH3 domain‑binding protein 1 (G3BP1) has been reported to be of importance in the occurrence and development of colon cancer. However, the underlying mechanisms remain largely unknown. Therefore, the aim of the present study was to investigate the role of Wnt/β‑catenin signaling in G3BP1‑mediated colon cancer progression. The expression of G3BP1 in colon tissues and cells was detected via reverse transcription‑quantitative PCR, western blotting and immunohistochemistry. Gain‑of‑function assays were performed in colon cancer RKO cells, which have a relatively low expression of G3BP1, while loss‑of‑function assays were performed in SW620 colon cancer cells, which have a relatively high expression of G3BP1. Cell proliferation, apoptosis and tumorigenesis were assessed using Cell Counting Kit‑8, flow cytometry and tumor‑bearing mice assays, respectively. The results demonstrated that G3BP1 expression was significantly upregulated in colon cancer tissues and cells compared with healthy colon tissues and cells. It was found that high expression of G3BP1 was closely associated with the poor prognosis and advanced clinical process in patients with colon cancer. Overexpression of G3BP1 in RKO cells enhanced their proliferative ability and decreased their apoptosis tendency, while knockdown of G3BP1 inhibited SW620 cell proliferation and induced apoptosis. In addition, G3BP1 interacted with β‑catenin and upregulated its expression and nuclear accumulation. It was identified that β‑catenin knockdown abolished the effects of G3BP1 on the enhancement of cell proliferation in vitro and tumor formation in vivo, as well as the inhibition of cell apoptosis. In conclusion, the present study demonstrated that G3BP1 promoted the progression of colon cancer by activating β‑catenin signaling, which provided novel evidence for the role of G3BP1 in colon cancer.

Citation

Yuanzhi Li, Jundong Wang, Sen Zhong, Jun Li, Weiliang Du. Overexpression of G3BP1 facilitates the progression of colon cancer by activating β‑catenin signaling. Molecular medicine reports. 2020 Nov;22(5):4403-4411