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      MZT2A promotes NSCLC viability and invasion by increasing Akt phosphorylation via the MOZART2 domain

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          Abstract

          Mitotic spindle organizing protein 2A (MZT2A) is localized at the centrosome and regulates microtubule nucleation activity in cells. This study assessed the role of MZT2A in non–small‐cell lung cancer (NSCLC). Differential MZT2A expression was bioinformatically assessed using TCGA database, the GEPIA database, and Kaplan‐Meier survival data to determine the association between MZT2A expression and NSCLC prognosis. Furthermore, NSCLC tissue specimens were evaluated by immunohistochemistry. MZT2A was overexpressed or knocked down in NSCLC cells using cDNA and siRNA, respectively. The cells were subjected to various assays and treated with the selective Akt inhibitor LY294002 or co‐transfected with galectin‐3‐binding protein (LGALS3BP) siRNA. MZT2A mRNA and protein levels were upregulated in NSCLC lesions and MTZ2A expression was associated with poor NSCLC prognosis. MZT2A protein was also highly expressed in NSCLC cells compared with the expression in normal bronchial cells. MZT2A expression promoted NSCLC cell viability and invasion, whereas MTZ2A siRNA had the opposite effect on NSCLC cells in vitro. At the protein level, MZT2A induced Akt phosphorylation, promoting NSCLC proliferation and invasion (but the selective Akt inhibitor blocked these effects) through upregulation of LGALS3BP via the MTZ2A MOZART2 domain, whereas LGALS3BP siRNA suppressed MTZ2A activity in NSCLC cells. The limited in vivo experiments confirmed the in vitro data. In conclusion, MZT2A exhibits oncogenic activity by activating LGALS3BP and Akt in NSCLC. Future studies will assess MTZ2A as a biomarker to predict NSCLC prognosis or as a target in the control of NSCLC progression.

          Abstract

          MZT2A induced Akt phosphorylation, promoting NSCLC proliferation and invasion through the upregulation of LGALS3BP via the MTZ2A MOZART2 domain. Future studies will assess MTZ2A as a biomarker to predict NSCLC prognosis or as a target to control NSCLC progression

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Cancer statistics, 2019

            Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2019)
            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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              Global cancer statistics, 2012.

              Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)
              Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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                Author and article information

                Contributors
                Xueshan Qiu:
                ORCID: https://orcid.org/0000-0001-9481-8249
                xsqiu@cmu.edu.cn
                Journal
                Journal ID (nlm-ta): Cancer Sci
                Journal ID (iso-abbrev): Cancer Sci
                Journal ID (doi): 10.1111/(ISSN)1349-7006
                Journal ID (publisher-id): CAS
                Title: Cancer Science
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1347-9032
                ISSN (Electronic): 1349-7006
                Publication date (Electronic): 07 April 2021
                Publication date (Print): June 2021
                Volume: 112
                Issue: 6 ( doiID: 10.1111/cas.v112.6 )
                Pages: 2210-2222
                Affiliations
                [ 1 ] Department of Pathology China Medical University Shenyang China
                [ 2 ] Departemt of Pathology Cancer Research Laboratory Chengde Medical College Chengde China
                [ 3 ] Department of Thoracic Surgery The First Affiliated Hospital of China Medical University Shenyang China
                [ 4 ] Department of Thoracic Surgery Shengjing Hospital of China Medical University Shenyang China
                [ 5 ] Department of Pathology The First Affiliated Hospital of China Medical University Shenyang China
                Author notes
                [*] [* ] Correspondence

                Xueshan Qiu, Department of Pathology, China Medical University, 77 Puhe Road, North Shenyang New Area, Shenyang, Liaoning 110122, China.

                Email: xsqiu@ 123456cmu.edu.cn

                Author information
                https://orcid.org/0000-0002-8676-4153
                https://orcid.org/0000-0001-9481-8249
                Article
                Publisher ID: CAS14900
                DOI: 10.1111/cas.14900
                PMC ID: 8177791
                PubMed ID: 33754417
                SO-VID: 4d0f6bed-c1cd-4367-ac69-0aa208123227
                Copyright © © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ 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
                Date revision received : 05 March 2021
                Date received : 18 November 2020
                Date accepted : 17 March 2021
                Page count
                Figures: 7, Tables: 1, Pages: 13, Words: 7235
                Categories
                Subject: Original Article
                Subject: Original Articles
                Subject: Carcinogenesis
                Custom metadata
                source-schema-version-number 2.0
                cover-date June 2021
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:04.06.2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: akt,lgals3bp,mzt2a,nsclc,prognosis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: akt, lgals3bp, mzt2a, nsclc, prognosis

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