CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis

Matilde Todaro, Miriam Gaggianesi, Veronica Catalano, Antonina Benfante, Flora Iovino, Mauro Biffoni, Tiziana Apuzzo, Isabella Sperduti, Silvia Volpe, Gianfranco Cocorullo, Gaspare Gulotta, Francesco Dieli, Ruggero De Maria, Giorgio Stassi

Research output: Contribution to journalArticlepeer-review


Cancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6- progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.

Original languageEnglish
Pages (from-to)342-356
Number of pages15
JournalCell Stem Cell
Issue number3
Publication statusPublished - Mar 6 2014

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics


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