The human oncogene SCL/TAL1 interrupting locus (STIL) promotes tumor growth through MAPK/ERK, PI3K/Akt and AMPK pathways in prostate cancer

Gene. 2019 Feb 20:686:220-227. doi: 10.1016/j.gene.2018.11.048. Epub 2018 Nov 16.

Abstract

The morbidity and mortality of prostate cancer (PCa) in China have increased obviously, which became the second leading cause of death in men with cancer. Hedgehog (Hh) signaling pathway is a key signaling pathway involved in the prostate cancer progression. The human oncogene SCL/TAL1 interrupting locus (STIL) can modulate the Hh signaling pathway, but its function in PCa has not been reported. Here, we showed that STIL was increased in high grade prostate cancer tissue. Knockdown of STIL in prostate cancer cells PC-3 and DU 145 significantly decreased the proliferation of cells and induced cellular apoptosis through casepase3/7 mediated pathway. Moreover, the colony formation ability was also inhibited when knockdown of STIL by lentivirus-mediated shRNA. Furthermore, the cellular signaling antibody array analysis revealed which signaling pathway was affected when silencing STIL. Altogether, we found that STIL could affect MAPK/ERK, PI3K/Akt and AMPK signaling pathways, thus promoting cellular proliferation, colony formation and suppressing cellular apoptosis in prostate cancer.

Keywords: AMPK; Cell cycle; Cell growth; MAPK; PI3K; Prostate cancer; STIL.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Signaling System*
  • Male
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • STIL protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases