Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation

Autor: Antoni Riera, Daniele V.F. Tauriello, Daniel Byrom, Elena Sancho, Sergio Palomo-Ponce, David Rossell, Peter Jung, María Virtudes Céspedes, Alexandre Calon, Marta Sevillano, Ramon Mangues, Joan Massagué, Eduard Batlle, Cristina Nadal, Xiang Zhang, Elisa Espinet, Mar Iglesias
Jazyk: angličtina
Předmět:
STAT3 Transcription Factor
Cancer Research
Stromal cell
Colorectal cancer
Receptor
Transforming Growth Factor-beta Type I
Protein Serine-Threonine Kinases
Biology
Article
Metastasis
Mice
03 medical and health sciences
HT29 Cells
0302 clinical medicine
Recurrence
Transforming Growth Factor beta
Cytokine Receptor gp130
Tumor Cells
Cultured
Tumor Microenvironment
medicine
Animals
Humans
Neoplasm Metastasis
030304 developmental biology
0303 health sciences
Tumor microenvironment
fungi
food and beverages
Cell Biology
Interleukin-11
Glycoprotein 130
medicine.disease
digestive system diseases
3. Good health
Oncology
030220 oncology & carcinogenesis
Cancer research
Stromal Cells
Signal transduction
Colorectal Neoplasms
Receptors
Transforming Growth Factor beta
Signal Transduction
Transforming growth factor
Zdroj: Cancer Cell. (5):571-584
ISSN: 1535-6108
DOI: 10.1016/j.ccr.2012.08.013
Popis: SummaryA 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.
Databáze: OpenAIRE
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