LIN28B promotes colon cancer progression and metastasis

Cancer Res. 2011 Jun 15;71(12):4260-8. doi: 10.1158/0008-5472.CAN-10-4637. Epub 2011 Apr 21.

Abstract

LIN28B is a homologue of LIN28 that induces pluripotency when expressed in conjunction with OCT4, SOX2, and KLF4 in somatic fibroblasts. LIN28B represses biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Recently, we have determined that LIN28B overexpression occurs in colon tumors. We conducted a comprehensive analysis of LIN28B protein expression in human colon adenocarcinomas. We found that LIN28B overexpression correlates with reduced patient survival and increased probability of tumor recurrence. To elucidate tumorigenic functions of LIN28B, we constitutively expressed LIN28B in colon cancer cells and evaluated tumor formation in vivo. Tumors with constitutive LIN28B expression exhibit increased expression of colonic stem cell markers LGR5 and PROM1, mucinous differentiation, and metastasis. Together, our findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Differentiation
  • Colonic Neoplasms / etiology*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Humans
  • Kruppel-Like Factor 4
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / physiology
  • RNA-Binding Proteins / physiology*

Substances

  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Lin28A protein, human
  • RNA-Binding Proteins