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      SKA1 promotes tumor metastasis via SAFB-mediated transcription repression of DUSP6 in clear cell renal cell carcinoma

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          Abstract

          The most hostile form of urologic cancer, clear cell renal cell carcinoma (ccRCC), has a high fatality rate and poor prognosis due to tumor metastasis at initial presentation. The complex process driving ccRCC metastasis is still unknown, though. In this study, we demonstrate that Spindle and kinetochore-associated protein 1 (SKA1) expression is significantly upregulated in ccRCC tissues and associated with aggressive clinicopathologic characteristics. Functionally, SKA1 knockdown on ccRCC cells reduced cancer cell motility both in vivo and in vitro research. These bioactivities of SKA1 may be brought on by its specific interaction with scaffold attachment factor B, according to the proposed mechanism (SAFB), which could further depress the transcription of dual specificity phosphatase 6 (DUSP6). Our findings may provide a new way of researching SKA1-regulated tumor metastasis, and indicate that SKA1 is a prospective therapeutic target for renal carcinoma.

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          Cancer statistics, 2020

          Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)
          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 population-based cancer occurrence. Incidence data (through 2016) 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 (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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            Analyzing real-time PCR data by the comparative C(T) method.

            Thomas D Schmittgen, Kenneth J Livak (2008)
            Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.
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              Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma

              Megan Wind-Rotolo, Sergio Bracarda, Howard Gurney … (2018)
              Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.
              Article 0 comments Cited 1468 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging (Albany NY)
                Journal ID (publisher-id): Aging
                Title: Aging (Albany NY)
                Publisher: Impact Journals
                ISSN (Electronic): 1945-4589
                Publication date Collection: 15 December 2022
                Publication date (Electronic): 02 December 2022
                Volume: 14
                Issue: 23
                Pages: 9679-9698
                Affiliations
                [1 ]Institute of Cancer Research, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830011, PR China
                [2 ]Department of Pharmacy, Xinjiang Medical University, Urumqi 830011, PR China
                [3 ]The Clinical Research Center of Breast Tumor and Thyroid Tumor in Xinjiang Autonomous Region, Urumqi 830011, PR China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Huibin Liu; email: 1047893820@qq.com, https://orcid.org/0000-0003-0673-6230
                Article
                Publisher ID: 204418 Publisher ID: 204418
                DOI: 10.18632/aging.204418
                PMC ID: 9792197
                PubMed ID: 36462498
                SO-VID: 78358f4c-f250-4a98-a698-b3e441ff7fc0
                Copyright © Copyright: © 2022 Pu et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 30 January 2022
                Date accepted : 19 November 2022
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Cell biology
                Keywords: ska1,ccrcc,safb,dusp6,metastasis
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: ska1, ccrcc, safb, dusp6, metastasis

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