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      GPC6 Promotes Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma

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          Abstract

          Nasopharyngeal carcinoma (NPC) is a highly metastatic tumor that occurs frequently in Southeast Asia, particularly including southern China. Epstein-Barr virus infection is well established as a primary cause of NPC; nevertheless, the mechanisms underlying NPC pathogenesis remain largely unknown. In our previous study, we conducted whole-genome sequencing to screen for genomic variations that were associated with NPC. Of the resultantly identified variations, glypican-6 ( GPC6), was shown, for the first time, to be frequently mutated in NPC. In the present study, we verified this finding and conducted a series of functional experiments, which demonstrated that GPC6 promotes the migration, invasion, and proliferation of NPC cells in vitro. Thus, the present study identified novel biological functions for GPC6 in NPC, and thus, showed that GPC6 may be a promising potential therapeutic target for this disease.

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          Most cited references48

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          Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma

          Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide and has no effective treatment, yet the molecular basis of hepatocarcinogenesis remains largely unknown. Here we report findings from a whole-genome sequencing (WGS) study of 88 matched HCC tumor/normal pairs, 81 of which are Hepatitis B virus (HBV) positive, seeking to identify genetically altered genes and pathways implicated in HBV-associated HCC. We find beta-catenin to be the most frequently mutated oncogene (15.9%) and TP53 the most frequently mutated tumor suppressor (35.2%). The Wnt/beta-catenin and JAK/STAT pathways, altered in 62.5% and 45.5% of cases, respectively, are likely to act as two major oncogenic drivers in HCC. This study also identifies several prevalent and potentially actionable mutations, including activating mutations of Janus kinase 1 ( JAK1 ), in 9.1% of patients and provides a path toward therapeutic intervention of the disease.
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            The genomic landscape of nasopharyngeal carcinoma.

            Nasopharyngeal carcinoma (NPC) has extremely skewed ethnic and geographic distributions, is poorly understood at the genetic level and is in need of effective therapeutic approaches. Here we determined the mutational landscape of 128 cases with NPC using whole-exome and targeted deep sequencing, as well as SNP array analysis. These approaches revealed a distinct mutational signature and nine significantly mutated genes, many of which have not been implicated previously in NPC. Notably, integrated analysis showed enrichment of genetic lesions affecting several important cellular processes and pathways, including chromatin modification, ERBB-PI3K signaling and autophagy machinery. Further functional studies suggested the biological relevance of these lesions to the NPC malignant phenotype. In addition, we uncovered a number of new druggable candidates because of their genomic alterations. Together our study provides a molecular basis for a comprehensive understanding of, and exploring new therapies for, NPC.
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              Role of metabolism in cancer cell radioresistance and radiosensitization methods

              Background Radioresistance is a major factor leading to the failure of radiotherapy and poor prognosis in tumor patients. Following the application of radiotherapy, the activity of various metabolic pathways considerably changes, which may result in the development of resistance to radiation. Main body Here, we discussed the relationships between radioresistance and mitochondrial and glucose metabolic pathways, aiming to elucidate the interplay between the tumor cell metabolism and radiotherapy resistance. In this review, we additionally summarized the potential therapeutic targets in the metabolic pathways. Short conclusion The aim of this review was to provide a theoretical basis and relevant references, which may lead to the improvement of the sensitivity of radiotherapy and prolong the survival of cancer patients.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2019
                24 June 2019
                : 10
                : 17
                : 3926-3932
                Affiliations
                [1 ]NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
                [2 ]The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Basic Medical Science, Central South University, Changsha, Hunan, China
                [3 ]Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
                [4 ]Department of Chemistry, University of North Dakota, Grand Forks, North Dakota, USA.
                Author notes
                ✉ Corresponding author: zengzhaoyang@ 123456csu.edu.cn

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav10p3926
                10.7150/jca.31345
                6692608
                f31e5f25-20d5-45c2-bc06-6b0da51c4f98
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 8 November 2018
                : 7 May 2019
                Categories
                Research Paper

                Oncology & Radiotherapy
                npc,gpc6,genomic variations,migration,invasion,proliferation
                Oncology & Radiotherapy
                npc, gpc6, genomic variations, migration, invasion, proliferation

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