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The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer
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- Liu, Na (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Xi An Jiao Tong Univ, Peoples R China
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- Cui, Weiyingqi (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
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- Jiang, Xia (author)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Hebei Med Univ, Peoples R China
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- (creator_code:org_t)
- Elsevier, 2019
- English.
- In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 104:5, s. 1153-1164
- Journal article (peer-reviewed)
Abstract
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- PurposeTo explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.Methods and MaterialsRho 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.ResultsRhoB 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.ConclusionsRhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- Liu, Na
- Cui, Weiyingqi
- Jiang, Xia
- Zhang, Zhiyong
- Gnosa, Sebastian
- Ali, Zaheer
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- Zhao, Zengren
- Ping, Jie
- Xie, Ning
- Kopsida, Maria
- Wang, Xin
- Sun, Xiao-Feng
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