SGK1 inhibition-induced autophagy impairs prostate cancer metastasis by reversing EMT

Weiwei Liu1, Xuchu Wang1, Yiyun Wang1

  • 1Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Abstract

Insights

Serum and glucocorticoid-regulated kinase 1 (SGK1) promotes prostate cancer metastasis by driving epithelial-mesenchymal transition (EMT). Inhibiting SGK1, especially with dual targeting of mTOR, reduces metastasis through autophagy, offering new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • SGK1 is recognized as a tumor-promoting gene.
  • Its specific role in cancer metastasis regulation remains largely unexplored.

Purpose of the Study:

  • To investigate the function and mechanisms of SGK1 in prostate cancer (PCa) metastasis.
  • To explore SGK1's role in regulating epithelial-mesenchymal transition (EMT) and autophagy.

Main Methods:

  • Utilized human PCa cell lines and PC3 xenografts.
  • Employed wound healing, migration, and invasion assays.
  • Performed western blotting, immunofluorescence, and immunohistochemistry.

Main Results:

  • SGK1 expression correlates with PCa progression and metastasis.
  • SGK1 inhibition attenuated EMT and metastasis; SGK1 overexpression promoted invasion and migration.
  • SGK1 inhibition induced anti-metastatic effects via autophagy-mediated EMT repression through Snail downregulation.
  • Dual inhibition of mTOR and SGK1 synergistically enhanced anti-metastatic effects.

Conclusions:

  • SGK1 acts as a novel metastasis-promoting gene in cancer.
  • Co-targeting SGK1 and autophagy presents a promising strategy to restrain cancer progression by amplifying anti-metastatic effects.

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