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

Aging (Albany NY). 2022 Dec 2;14(23):9679-9698. doi: 10.18632/aging.204418. Epub 2022 Dec 2.

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.

Keywords: DUSP6; SAFB; SKA1; ccRCC; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma*
  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Dual Specificity Phosphatase 6
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • Matrix Attachment Region Binding Proteins*
  • Neoplasm Metastasis
  • Nuclear Matrix-Associated Proteins
  • Receptors, Estrogen

Substances

  • Dual Specificity Phosphatase 6
  • SAFB protein, human
  • Receptors, Estrogen
  • Nuclear Matrix-Associated Proteins
  • Matrix Attachment Region Binding Proteins
  • DUSP6 protein, human
  • SKA1 protein, human