Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation Journal Article
| Authors: | Calon, A.; Espinet, E.; Palomo-Ponce, S.; Tauriello, D. V. F.; Iglesias, M.; Céspedes, M. V.; Sevillano, M.; Nadal, C.; Jung, P.; Zhang, X. H. F.; Byrom, D.; Riera, A.; Rossell, D.; Mangues, R.; Massague, J.; Sancho, E.; Batlle, E. |
| Article Title: | Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation |
| Abstract: | A large proportion of colorectal cancers (CRCs) display mutational inactivation of the TGF-β pathway, yet, paradoxically, they are characterized by elevated TGF-β production. Here, we unveil a prometastatic program induced by TGF-β in the microenvironment that associates with a high risk of CRC relapse upon treatment. The activity of TGF-β on stromal cells increases the efficiency of organ colonization by CRC cells, whereas mice treated with a pharmacological inhibitor of TGFBR1 are resilient to metastasis formation. Secretion of IL11 by TGF-β-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3 signaling in tumor cells. This crosstalk confers a survival advantage to metastatic cells. The dependency on the TGF-β stromal program for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC. © 2012 Elsevier Inc. |
| Keywords: | signal transduction; controlled study; human cell; cancer risk; nonhuman; antineoplastic agent; colorectal cancer; animal cell; mouse; animals; mice; cell survival; stat3 protein; transforming growth factor beta; animal experiment; animal model; relapse; recurrence; tumor cells, cultured; colorectal neoplasms; protein-serine-threonine kinases; nucleotide sequence; cancer cell; neoplasm metastasis; fibroblast; receptors, transforming growth factor beta; stroma; cytokine receptor gp130; stat3 transcription factor; metastasis potential; microenvironment; stromal cells; ht29 cells; interleukin 1; tumor microenvironment; interleukin-11 |
| Journal Title: | Cancer Cell |
| Volume: | 22 |
| Issue: | 5 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2012-11-13 |
| Start Page: | 571 |
| End Page: | 584 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2012.08.013 |
| PROVIDER: | scopus |
| PUBMED: | 23153532 |
| PMCID: | PMC3512565 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 December 2012" - "CODEN: CCAEC" - "Source: Scopus" |
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