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The Critical Role o...
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Liu, NaLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Xi An Jiao Tong Univ, Peoples R China
(author)
The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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Elsevier,2019
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:liu-159237
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-159237URI
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https://doi.org/10.1016/j.ijrobp.2019.04.021DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding Agencies|Swedish Cancer Foundation; Swedish Research Council; Health Research Council in southeast Sweden; Oncology Clinics in Linkoping; National Natural Science Foundation of China [81872397]; State Key Laboratory Cancer Biology Open Foundation [CBSKL201730]; Xian Technology Foundation [201805094YX2SF28(6)]; International Science and Technology Cooperation Programme of China [2014DFA31150]; Medical Research Council [MR/N012097/1]; Cancer Research UK [C37/A12011, C37/A18784]; Breast Cancer Now [2012MayPR070, 2012NovPhD016]; Cancer Research UK Imperial Centre; Imperial Experimental Cancer Medicine Centre; National Institute for Health Research Imperial Biomedical Research Centre
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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.
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Cui, WeiyingqiLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)n/a
(author)
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Jiang, XiaLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Hebei Med Univ, Peoples R China
(author)
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Zhang, ZhiyongFourth Mil Med Univ, Peoples R China
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Gnosa, SebastianLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)sebgn30
(author)
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Ali, ZaheerLinköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten(Swepub:liu)aliza36
(author)
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Jensen, LasseLinköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi(Swepub:liu)larje86
(author)
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Jönsson, Jan-IngvarLinköpings universitet,Avdelningen för hematopoes och utvecklingsbiologi,Medicinska fakulteten(Swepub:liu)janjo86
(author)
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Blockhuys, StephanieLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)n/a
(author)
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Lam, Eric W-FImperial Coll London, England
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Zhao, ZengrenHebei Med Univ, Peoples R China
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Ping, JieLinköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)jiepi15
(author)
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Xie, NingXi An Jiao Tong Univ, Peoples R China
(author)
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Kopsida, MariaLinköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)marko66
(author)
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Wang, XinFourth Mil Med Univ, Peoples R China
(author)
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Sun, Xiao-FengLinköpings universitet,Avdelningen för Kirurgi, Ortopedi och Onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)xiasu45
(author)
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Linköpings universitetInstitutionen för klinisk och experimentell medicin
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In:International Journal of Radiation Oncology, Biology, Physics: Elsevier104:5, s. 1153-11640360-30161879-355X
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Liu, Na
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Xie, Ning
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Wang, Xin
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Sun, Xiao-Feng
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