4.6 Article

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

Journal

AGING-US
Volume 14, Issue 23, Pages 9679-9698

Publisher

IMPACT JOURNALS LLC

Keywords

SKA1; ccRCC; SAFB; DUSP6; metastasis

Funding

  1. National Natural Science Foundation of China [81760453]
  2. Foundation for Xinjiang Talent [2019XS15]

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Clear cell renal cell carcinoma (ccRCC) is a highly aggressive urologic cancer with high fatality rate and poor prognosis due to tumor metastasis at initial presentation. This study found that Spindle and kinetochore-associated protein 1 (SKA1) expression is significantly upregulated in ccRCC tissues and associated with aggressive clinicopathologic characteristics. Functional study revealed that SKA1 knockdown in ccRCC cells reduced cancer cell motility in both in vivo and in vitro research, potentially through its specific interaction with scaffold attachment factor B and subsequent transcriptional repression of dual specificity phosphatase 6 (DUSP6).
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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