3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Transcriptional Activation of Gstp1 by MEK/ERK Signaling Confers Chemo-Resistance to Cisplatin in Lung Cancer Stem Cells

      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

          Lung cancer management remains a challenge due to its asymptomatic and late presentation when it is metastatic. The clinical response to the first-line platinum-based chemotherapy in patients with advanced lung cancer is disappointing due to the development of chemoresistance. Chemoresistance is a complex phenomenon. Mechanistic research using experimental models has yielded limited clinical results to help increase understanding for overcoming resistance. While the role of lung CSCs in conferring multidrug resistance has been postulated, experimental evidence remains associative and lacks in depth mechanistic inquisition. In the present study, using mouse and human lung adenocarcinoma cell lines and their respective paired CSC derivative cell lines that we generated, we identified cancer stem cell component of lung adenocarcinoma as the source that confers multidrug resistance phenotype. Mechanistically, Gstp1 confers cisplatin resistance in mouse and human lung CSC models, both in vitro and in vivo. Further, transcriptional activation of Gstp1 expression by MEK/ERK signaling underlies cisplatin resistance in lung CSC cells. Moreover, we show that GSTP1 expression is a poor diagnostic and prognostic marker for human lung adenocarcinoma, thus is of high clinical relevance. Taken together, we have provided mechanistic understanding of the lung CSC in mediating chemoresistance.

          Related collections

          Most cited references34

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

          A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers.

          The validation of tumor, node, metastasis staging system in terms of prognosis is an indispensable part of establishing a better staging system in lung cancer. In 2005, 387 Japanese institutions submitted information regarding the prognosis and clinicopathologic profiles of patients who underwent pulmonary resections for primary lung neoplasms in 1999 to the Japanese Joint Committee of Lung Cancer Registry. The data of 13,010 patients with only lung carcinoma histology (97.6%) were analyzed in terms of prognosis and clinicopathologic characteristics. The 5-year survival rate of the entire group was 61.4%. For the small cell histology (n = 390), the 5-year survival rates according to clinical (c) and pathologic (p) stages were as follows: 58.8% (n = 161) and 58.3% (n = 127) for IA, 58.0% (n = 77) and 60.2% (n = 79) for IB, 47.1% (n = 17) and 40.6% (n = 29) for IIA, 25.3% (n = 38) and 41.1% (n = 29) for IIB, 29.0% (n = 61) and 28.3% (n = 60) for IIIA, 36.3% (n = 19) and 34.6% (n = 40) for IIIB, and 27.8% (n = 12) and 30.8% for IV (n = 13). For the non-small cell histology (n = 12,620), the 5-year survival rates according to c-stage and p-stage were as follows: 77.3% (n = 5642) and 83.9% (n = 4772) for IA, 59.8% (n = 3081) and 66.3% (n = 2629) for IB, 54.1% (n = 205) and 61.0% (n = 361) for IIA, 43.9% (n = 1227) and 47.4% (n = 1330) for IIB, 38.3% (n = 1628) and 32.8% (n = 1862) for IIIA, 32.6% (n = 526) and 29.6% (n = 1108) for IIIB, and 26.5% (n = 198) and 23.1% (n = 375) for IV. Adenocarcinoma, female gender, and age less than 50 years were significant favorable prognostic factors. This large registry study provides benchmark prognostic statistics for lung cancer. The prognostic difference between stages IB and IIA was small despite different stages. Otherwise, the present tumor, node, metastasis staging system well characterizes the stage-specific prognoses.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            An enzyme from rat liver catalysing conjugations with glutathione.

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

              The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer.

              Glutathione S-transferase P is abundantly expressed in some mammalian tissues, particularly those associated with malignancies. While the enzyme can catalyze thioether bond formation between some electrophilic chemicals and GSH, novel nondetoxification functions are now ascribed to it. This review summarizes recent material that implicates GSTP in mediating S-glutathionylation of specific clusters of target proteins and in reactions that define a negative regulatory role in some kinase pathways through ligand or protein:protein interactions. It is becoming apparent that GSTP participates in the maintenance of cellular redox homeostasis through a number of convergent and divergent mechanisms. Moreover, drug platforms that have GSTP as a target have produced some interesting preclinical and clinical candidates. Copyright © 2011 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                11 June 2019
                2019
                : 9
                : 476
                Affiliations
                [1] 1Laboratory of Translational Cancer Stem Cell Research, Institute of Life Sciences, Chongqing Medical University , Chongqing, China
                [2] 2State Key Laboratory of Ultrasound Engineering in Medicine, Chongqing Medical University and the Ministry of Science and Technology , Chongqing, China
                Author notes

                Edited by: Luisa Lanfrancone, Istituto Europeo di Oncologia s.r.l., Italy

                Reviewed by: Kenneth K. W. To, The Chinese University of Hong Kong, China; Sabarish Ramachandran, Texas Tech University Health Sciences Center, United States

                *Correspondence: Jianyu Wang wjy2003123@ 123456163.com

                This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2019.00476
                6584806
                31263672
                444684be-5ce8-4e04-a130-53baf61d855e
                Copyright © 2019 Li, Ye, Liu, Kong, Sun, Liu, Wang and Xing.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 24 November 2018
                : 20 May 2019
                Page count
                Figures: 9, Tables: 2, Equations: 0, References: 45, Pages: 14, Words: 8264
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81602596
                Award ID: 81672908
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                gstp1,cancer stem cell,chemotherapeutic resistance,mek/erk signaling pathway,lung adenocarcinoma

                Comments

                Comment on this article