Pseudopod-associated protein KIF20B promotes Gli1-induced epithelial-mesenchymal transition modulated by pseudopodial actin dynamic in human colorectal cancer

Mol Carcinog. 2018 Jul;57(7):911-925. doi: 10.1002/mc.22812. Epub 2018 Apr 10.

Abstract

Kinesin family member 20B (KIF20B) has been reported to have an oncogenic role in bladder and hepatocellular cancer cells, but its role in colorectal cancer (CRC) progression remains unclear. In this study, we assessed the mRNA and protein levels of KIF20B in CRC tissues using qRT-PCR and immunohistochemistry, respectively. KIF20B was overexpressed in CRC tissues and was associated with cancer invasion and metastasis. Mechanistically, KIF20B overexpression promoted the epithelial-mesenchymal transition (EMT) process mediated by glioma-associated oncogene 1 (Gli1) as well as CRC cell migration and invasion. Interestingly, KIF20B was localized in pseudopod protrusions of CRC cells and influenced the formation of cell protrusions, especially the EMT-related invadopodia. Moreover, intracellular actin dynamic participated in the modulation of the Gli1-mediated EMT and EMT-related cell pseudopod protrusion formation induced by KIF20B. We identified a role for KIF20B in CRC progression and revealed a correlation between KIF20B expression in CRC tissues and patient prognosis. The underlying mechanism was associated with the Gli1-mediated EMT and EMT-related cell protrusion formation modulated by intracellular actin dynamic. Thus, KIF20B may be a potential biomarker and promising treatment target for CRC.

Keywords: EMT; Gli1; KIF20B; colorectal cancer; cytoskeleton dynamic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kinesins / genetics*
  • Male
  • Prognosis
  • Zinc Finger Protein GLI1 / genetics*

Substances

  • Actins
  • GLI1 protein, human
  • Zinc Finger Protein GLI1
  • KIF20B protein, human
  • Kinesins