9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Rho GDP‐dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Rho GDP‐dissociation inhibitor α (Rho GDIα) is an essential regulator for Rho GTPases. Although Rho GDI α may serve as an oncogene in colorectal cancer ( CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of Rho GDIα in CRC progression. We founded that downregulation of Rho GDIα repressed CRC cell proliferation, motility, and invasion. Overexpression of Rho GDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that Rho GDIα could promote telomeric repeat factor 1 ( TRF1) expression through the phosphatidylinositol 3‐kinase–protein kinase B signal pathway. Moreover, Rho GDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between Rho GDIα and TRF1, and revealed that Rho GDIα and TRF1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that Rho GDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.

          Related collections

          Most cited references31

          • Record: found
          • Abstract: found
          • Article: not found

          Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice.

          Aged humans sustain a high rate of epithelial cancers such as carcinomas of the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. Among the many factors that may contribute to this species variance are differences in telomere length and regulation. Telomeres comprise the nucleoprotein complexes that cap the ends of eukaryotic chromosomes and are maintained by the reverse transcriptase, telomerase. In human cells, insufficient levels of telomerase lead to telomere attrition with cell division in culture and possibly with ageing and tumorigenesis in vivo. In contrast, critical reduction in telomere length is not observed in the mouse owing to promiscuous telomerase expression and long telomeres. Here we provide evidence that telomere attrition in ageing telomerase-deficient p53 mutant mice promotes the development of epithelial cancers by a process of fusion-bridge breakage that leads to the formation of complex non-reciprocal translocations--a classical cytogenetic feature of human carcinomas. Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The 'invisible hand': regulation of RHO GTPases by RHOGDIs.

            The 'invisible hand' is a term originally coined by Adam Smith in The Theory of Moral Sentiments to describe the forces of self-interest, competition and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              GDIs: central regulatory molecules in Rho GTPase activation.

              The GDP dissociation inhibitors (GDIs) are pivotal regulators of Rho GTPase function. GDIs control the access of Rho GTPases to regulatory guanine nucleotide exchange factors and GTPase-activating proteins, to effector targets and to membranes where such effectors reside. We discuss here our current understanding of how Rho GTPase-GDI complexes are regulated by various proteins, lipids and enzymes that exert GDI displacement activity. We propose that phosphorylation mediated by diverse kinases might provide a means of controlling and coordinating Rho GTPase activation.
                Bookmark

                Author and article information

                Contributors
                hjunjiu@mail.sysu.edu.cn
                fanglk3@mail.sysu.edu.cn
                Journal
                Cancer Sci
                Cancer Sci
                10.1111/(ISSN)1349-7006
                CAS
                Cancer Science
                John Wiley and Sons Inc. (Hoboken )
                1347-9032
                1349-7006
                31 May 2017
                July 2017
                : 108
                : 7 ( doiID: 10.1111/cas.2017.108.issue-7 )
                : 1293-1302
                Affiliations
                [ 1 ] Department of Colorectal SurgeryThe Sixth Affiliated Hospital of Sun Yat‐sen University GuangzhouChina
                [ 2 ] Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseaseThe Sixth Affiliated Hospital of Sun Yat‐sen University GuangzhouChina
                [ 3 ] State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat‐sen University GuangzhouChina
                [ 4 ] Key Laboratory of Gene Engineering of the Ministry of Education School of Life SciencesSun Yat‐sen University GuangzhouChina
                Author notes
                [*] [* ] Correspondence

                Lekun Fang, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat‐sen University, Guangzhou 510655, China.

                Tel./Fax: +86‐020‐38455534;

                E‐mail: fanglk3@ 123456mail.sysu.edu.cn

                and

                Junjiu Huang, Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat‐sen University, Guangzhou 510275, China.

                Tel./Fax: +86‐020‐39943778;

                E‐mail: hjunjiu@ 123456mail.sysu.edu.cn

                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-0296-292X
                Article
                CAS13259
                10.1111/cas.13259
                5497806
                28417530
                8deb30d6-5525-499c-aa6b-cbff20570278
                © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 27 December 2016
                : 06 April 2017
                : 08 April 2017
                Page count
                Figures: 4, Tables: 3, Pages: 10, Words: 7133
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31601179
                Award ID: 81602429
                Award ID: 81630072
                Funded by: Ministry of Science and Technology of China
                Award ID: 2015CB554000
                Funded by: National Key Technology R&D Program
                Award ID: 2014BAI09B06
                Funded by: Natural Science Foundation of Guangdong Province
                Award ID: 2016A030310209
                Categories
                Original Article
                Original Articles
                Carcinogenesis
                Custom metadata
                2.0
                cas13259
                July 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.2 mode:remove_FC converted:05.07.2017

                Oncology & Radiotherapy
                colorectal cancer,prognosis,rhogdiα,telomere,trf1
                Oncology & Radiotherapy
                colorectal cancer, prognosis, rhogdiα, telomere, trf1

                Comments

                Comment on this article