KRASG12 mutant induces the release of the WSTF/NRG3 complex, and contributes to an oncogenic paracrine signaling pathway

Academic Article

Abstract

  • It remains unclear how the signals of mutant KRASG12 in the transformed cells spread to the surrounding non-mutated cells and changes the microenvironment to promote tumor formation. We identified that Williams-Beuren syndrome transcription factor (WSTF), a non-secretory protein, was released in complex with secretory proteinneuregulin- 3 (NRG3). The KRASG12 mutant activates the transcription of NRG3. The WSTF/NRG3 in extracellular space could activate oncogenic pathways in normal colon cells carrying wild type KRAS and endow them with the ability to express NRG3 and release WSTF/NRG3. Extracellular WSTF/NRG3 promotes the formation of colon tumors. Blockade of extracellular WSTF could restore cetuximab sensitivity of colon cancer cells with mutant KRAS. The appearance of WSTF/NRG3 in serum and urine correlates with a colon tumor carrying a KRASG12 mutant. In summary, our demonstration provides a new pathway to our understanding of the biological development of complex diseases.
  • Authors

    Published In

  • Oncotarget  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 28111002
  • Author List

  • Liu Y; Wang SQ; Long YH; Chen S; Li YF; Zhang JH
  • Start Page

  • 53153
  • End Page

  • 53164
  • Volume

  • 7
  • Issue

  • 33