The role of SOX family transcription factors in gastric cancer

Int J Biol Macromol. 2021 Jun 1:180:608-624. doi: 10.1016/j.ijbiomac.2021.02.202. Epub 2021 Mar 1.

Abstract

Gastric cancer (GC) is a leading cause of death worldwide. GC is the third-most common cause of cancer-related death after lung and colorectal cancer. It is also the fifth-most commonly diagnosed cancer. Accumulating evidence has revealed the role of signaling networks in GC progression. Identification of these molecular pathways can provide new insight into therapeutic approaches for GC. Several molecular factors involved in GC can play both onco-suppressor and oncogene roles. Sex-determining region Y (Sry)-box-containing (SOX) family members are transcription factors with a well-known role in cancer. SOX proteins can bind to DNA to regulate cellular pathways via a highly conserved domain known as high mobility group (HMG). In the present review, the roles of SOX proteins in the progression and/or inhibition of GC are discussed. The dual role of SOX proteins as tumor-promoting and tumor-suppressing factors is highlighted. SOX members can affect upstream mediators (microRNAs, long non-coding RNAs and NF-κB) and down-stream mediators (FAK, HIF-1α, CDX2 and PTEN) in GC. The possible role of anti-tumor compounds to target SOX pathway members in GC therapy is described. Moreover, SOX proteins may be used as diagnostic or prognostic biomarkers in GC.

Keywords: Cancer therapy; Gastric cancer; High mobility group domain; SOX family members.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Molecular Targeted Therapy / methods
  • SOX Transcription Factors / antagonists & inhibitors
  • SOX Transcription Factors / genetics*
  • SOX Transcription Factors / metabolism
  • SOXB1 Transcription Factors / antagonists & inhibitors
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • SOX Transcription Factors
  • SOXB1 Transcription Factors