Dependency of colorectal cancer on a TGF-beta-driven programme in stromal cells for metastasis initiation

By A. Calon, Elisa Espinet, Sergio Palomo-Ponce, Daniele V. F. Tauriello, M. Iglesias, M. V. Céspedes, Marta Sevillano, C. Nadal, P. Jung, X. Zhang and 7 more. Cancer Cell, 2012

1,037 citations recorded by the source corpus.

SUMMARY A large proportion of colorectal cancers (CRCs) display mutational inactivation of the TGF-beta pathway yet paradoxically, they are characterized by elevated TGF-beta production. Here, we unveil a prometastatic programme induced by TGF-beta in the microenvironment that associates with a high-risk of CRC relapse upon treatment. The activity of TGF-beta 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-beta-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3 signalling in tumour cells. This crosstalk confers a survival advantage to metastatic cells. The dependency on the TGF-beta stromal programme for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC.

Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/974bc4d7a58a287a1f1ea9d34c7ba09fcb2f3847

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In Molecular Biology

1. E. Batlle
2. M. Nieto
3. J. Massagué
4. Thordur Oskarsson
5. Florian Markowetz
6. F. Greten
7. D. Tuveson
8. D. Öhlund

In Oncology

1. J. Massagué
2. E. Batlle
3. Thordur Oskarsson
4. S. Grivennikov
5. F. Greten
6. M. Nieto
7. Louis Vermeulen
8. D. Tuveson

In Pathology and Forensic Medicine

1. J. Massagué

Citations in the corpus

• Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “Moreover, IL-11 is involved in the recruitment of TGFβ driven and producing fibroblasts, which supports tumor invasion and immune escape in the subset of colon cancer with the worst clinical prognosis (Calon et al., 2012; Calon et al., 2015).”
• Fibroblast heterogeneity in the cancer wound (2014, background): “TGF- response in CAFs led to secretion of IL-11, which in turn can induce GP130/STAT3 signaling in neoplastic cells to support tumor initiation and accelerate metastasis (Calon et al., 2012).”
• Metastatic Stem Cells: Sources, Niches, and Vital Pathways (2014, background): “As metastatic lesions grow, the cancer cells recruit TAMs, myeloid precursors, and mesenchymal cells that establish paracrine loops feeding back to the cancer cells with various survival and self-renewal factors (Figure 7; Acharyya et al., 2012; Calón et al., 2012; Joyce and Pollard, 2009; Vermeulen”