ILEI: A Cytokine Essential for EMT, Tumor Formation, and Late Events in Metastasis in Epithelial Cells

Cancer Cell. 2006 Sep;10(3):227-39. doi: 10.1016/j.ccr.2006.07.020.

Abstract

Erk/MAPK and TGFbeta signaling cause epithelial to mesenchymal transition (EMT) and metastasis in mouse mammary epithelial cells (EpH4) transformed with oncogenic Ras (EpRas). In trials to unravel underlying mechanisms, expression profiling for EMT-specific genes identified a secreted interleukin-related protein (ILEI), upregulated exclusively at the translational level. Stable overexpression of ILEI in EpH4 and EpRas cells caused EMT, tumor growth, and metastasis, independent of TGFbeta-R signaling and enhanced by Bcl2. RNAi-mediated knockdown of ILEI in EpRas cells before and after EMT (EpRasXT) prevented and reverted TGFbeta-dependent EMT, also abrogating metastasis formation. ILEI is overexpressed and/or altered in intracellular localization in multiple human tumors, an event strongly correlated to invasion/EMT, metastasis formation, and survival in human colon and breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Transplantation
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Prognosis
  • Protein Biosynthesis / genetics
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Survival Rate
  • Time Factors
  • Transforming Growth Factor beta / metabolism

Substances

  • Cytokines
  • FAM3C protein, human
  • Fam3c protein, mouse
  • Neoplasm Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta