Arl4c is a key regulator of tubulogenesis and tumourigenesis as a target gene of Wnt-β-catenin and growth factor-Ras signalling

J Biochem. 2017 Jan;161(1):27-35. doi: 10.1093/jb/mvw069. Epub 2016 Nov 8.


Epithelial tubular morphogenesis (tubulogenesis) is a fundamental morphogenetic process of many epithelial organs. In this developmental process, epithelial cells migrate, proliferate, polarize and differentiate towards surrounding mesenchymal tissue to form tubule structures. Although epithelial tissue structures are basically stable in the postnatal period, epithelial cells regain highly proliferative and invasive potentials within mesenchymal tissue during tumour formation (tumourigenesis). Therefore, there must be a common molecular basis orchestrating the cellular behaviours involved in both tubulogenesis and tumourigenesis. ADP-ribosylation factor (Arf)-like protein 4c (Arl4c), which belongs to the small GTP-binding protein family, is expressed by the simultaneous activation of Wnt-β-catenin and growth factor-Ras-mitogen-activated protein kinase signalling, was identified as an essential regulator of tubulogenesis. Arl4c expression was also involved in the tumour formation of colorectal and lung cancers. In this review, we focus on Arl4c as a novel Wnt signal target molecule that links epithelial tubulogenesis to tumourigenesis.

Keywords: Arl4c; Wnt; growth factor; tubulogenesis; tumourigenesis.

Publication types

  • Review

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Humans
  • Kidney Tubules / metabolism*
  • Kidney Tubules / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Oncogene Protein p21(ras) / genetics
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Wnt Proteins
  • beta Catenin
  • ADP-Ribosylation Factors
  • ARL4C protein, human
  • Oncogene Protein p21(ras)