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

Int J Radiat Oncol Biol Phys. 2019 Aug 1;104(5):1153-1164. doi: 10.1016/j.ijrobp.2019.04.021. Epub 2019 Apr 27.


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

Methods and materials: Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Cell Line
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / radiotherapy
  • Down-Regulation
  • Forkhead Box Protein M1 / metabolism*
  • Gene Knockout Techniques
  • Humans
  • In Vitro Techniques
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Radiation Tolerance*
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / radiotherapy
  • Signal Transduction
  • Zebrafish
  • rhoB GTP-Binding Protein / genetics
  • rhoB GTP-Binding Protein / metabolism*


  • Biomarkers, Tumor
  • Forkhead Box Protein M1
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-akt
  • rhoB GTP-Binding Protein