The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer

失调的 RhoB 信号通路在结直肠癌放射抗性中的关键作用

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作者:Na Liu, Weiyingqi Cui, Xia Jiang, Zhiyong Zhang, Sebastian Gnosa, Zaheer Ali, Lasse Jensen, Jan-Ingvar Jönsson, Stéphanie Blockhuys, Eric W-F Lam, Zengren Zhao, Jie Ping, Ning Xie, Maria Kopsida, Xin Wang, Xiao-Feng Sun

Conclusions

RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.

Purpose

To explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.

Results

RhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry-based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors. Conclusions: RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.

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