Kindlin‑2 suppresses cervical cancer cell migration through AKT/mTOR‑mediated autophagy induction

Oncol Rep. 2020 Jul;44(1):69-76. doi: 10.3892/or.2020.7603. Epub 2020 May 4.

Abstract

Kindlin‑2 plays a carcinogenic or tumor‑suppressor role in various tumors. However, its role in cervical cancer remains unclear. In the present study, kindlin‑2 expression was first analyzed using public expression data and clinical specimens. It was revealed that kindlin‑2 was downregulated in cervical cancer tissues, and low expression of kindlin‑2 was associated with poor disease‑free survival. In addition, kindlin‑2 was overexpressed and knocked down in two cell lines to study its effect in cervical cancer cells. The results revealed that kindlin‑2 promoted cell autophagy and inactivated AKT/mTOR signaling. Rescue experiments indicated that the regulation of autophagy by kindlin‑2 was dependent on the AKT/mTOR signaling pathway. Furthermore, it was revealed that kindlin‑2 inhibited cell migration, and autophagy was required for this process. Collectively, these findings revealed the role and mechanism of kindlin‑2 in the autophagy and migration of cervical cancer cells.

Keywords: kindlin-2; autophagy; metastasis; AKT/mTOR; cervical cancer.

MeSH terms

  • Adult
  • Aged
  • Autophagy
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sequence Analysis, RNA
  • Signal Transduction
  • Survival Analysis
  • TOR Serine-Threonine Kinases / metabolism
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / mortality*

Substances

  • FERMT2 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases