Details

Autor(en) / Beteiligte

• Bauer, Jessica
• Emon, Md Abul Bashar
• Staudacher, Jonas J
• Thomas, Alexandra L
• Zessner-Spitzenberg, Jasmin
• Mancinelli, Georgina
• Krett, Nancy
• Saif, M Taher
• Jung, Barbara

Titel

Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer associated fibroblast-mediated prometastatic activin A signaling

Ist Teil von

• Scientific reports, 2020-01, Vol.10 (1), p.50-50, Article 50

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Colorectal cancer (CRC) is the second deadliest cancer in the US due to its propensity to metastasize. Stromal cells and especially cancer-associated fibroblasts (CAF) play a critical biophysical role in cancer progression, but the precise pro-metastatic mechanisms are not clear. Activin A, a TGF-β family member, is a strong pro-metastatic cytokine in the context of CRC. Here, we assessed the link between biophysical forces and pro-metastatic signaling by testing the hypothesis that CAF-generated mechanical forces lead to activin A release and associated downstream effects. Consistent with our hypothesis, we first determined that stromal activin A secretion increased with increasing substrate stiffness. Then we found that stromally-secreted activin A induced ligand-dependent CRC epithelial cell migration and epithelial to mesenchymal transition (EMT). In addition, serum activin A levels are significantly increased in metastatic (stage IV) CRC patients (1.558 ng/ml versus 0.4179 ng/ml, p < 0.05). We propose that increased tumor microenvironment stiffness leads to stromal cell-mediated TGF-β family signaling relying on the induction and utilization of activin A signaling.