BMX/Etk promotes cell proliferation and tumorigenicity of cervical cancer cells through PI3K/AKT/mTOR and STAT3 pathways

Oncotarget. 2017 Jul 25;8(30):49238-49252. doi: 10.18632/oncotarget.17493.

Abstract

Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be involved in cell proliferation, differentiation, apoptosis, migration and invasion in several types of tumors, but its role in cervical carcinoma remains poorly understood. In this study, we showed that BMX expression exhibits a gradually increasing trend from normal cervical tissue to cervical cancer in situ and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell proliferation was significantly decreased. Knockdown of BMX in HeLa and SiHa cervical cancer cell lines using two different silencing technologies, TALEN and shRNA, inhibited cell growth in vitro and suppressed xenograft tumor formation in vivo, whereas overexpression of BMX in the cell line C-33A significantly increased cell proliferation. Furthermore, a mechanism study showed that silencing BMX blocked cell cycle transit from G0/G1 to S or G2/M phase, and knockdown of BMX inhibited the expression of p-AKT and p-STAT3. These results suggested that BMX can promote cell proliferation through PI3K/AKT/mTOR and STAT3 signaling pathways in cervical cancer cells.

Keywords: AKT; BMX; STAT3; cell proliferation; cervical carcinoma.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cervix Uteri / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Heterografts
  • Humans
  • Mice
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • BMX protein, human
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt