Critical role of HMGA proteins in cancer cell chemoresistance

J Mol Med (Berl). 2017 Apr;95(4):353-360. doi: 10.1007/s00109-017-1520-x. Epub 2017 Mar 14.

Abstract

The high-mobility group A (HMGA) proteins are frequently overexpressed in human malignancies and correlate with the presence of metastases and reduced patient survival. Here, we highlight the main studies evidencing a critical role of HMGA in chemoresistance, mainly by activating Akt signaling, impairing p53 activity, and regulating the expression of microRNAs that target genes involved in the susceptibility of cancer cells to antineoplastic agents. Therefore, these studies account for the association of HMGA overexpression with patient poor outcome, indicating the impairment of HMGA as a fascinating perspective for effectively improving cancer therapy.

Keywords: Apoptosis; Chemoresistance; DNA repair; HMGA; miRNAs.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic* / drug effects
  • HMGA Proteins / genetics*
  • HMGA Proteins / metabolism
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • HMGA Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt