Targeting STAT3 Signaling in COL1+ Fibroblasts Controls Colitis-Associated Cancer in Mice

Heichler C, Schmied A, Enderle K, Scheibe K, Murawska M, Schmid B, Waldner M, Neurath M, Neufert C (2022)

Publication Type: Journal article

Publication year: 2022


Book Volume: 14

Article Number: 1472

Journal Issue: 6

DOI: 10.3390/cancers14061472


Colorectal cancer (CRC) is a common disease and has limited treatment options. The importance of cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) in CRC has been increasingly recognized. However, the role of CAF subsets in CRC is hardly understood and opposing functions of type I (COL1+) vs. type VI (COL6+) collagen-expressing subsets were reported before with respect to NFκB-related signaling. Here, we have focused on COL1+ fibroblasts, which represent a frequent CAF population in CRC and studied their role upon STAT3 activation in vivo. Using a dual strategy with a conditional gain-of-function and a conditional loss-of-function approach in an in vivo model of colitis-associated cancer, tumor development was evaluated by different readouts, including advanced imaging methodologies, e.g., light sheet microscopy and CT-scan. Our data demonstrate that the inhibition of STAT3 activation in COL1+ fibroblasts reduces tumor burden, whereas the constitutive activation of STAT3 promotes the development of inflammation-driven CRC. In addition, our work characterizes the co-expression and distribution of type I and type VI collagen by CAFs in inflammation-associated colorectal cancer using reporter mice. This work indicates a critical contribution of STAT3 signaling in COL1+ CAFs, suggesting that the blockade of STAT3 activation in type I collagen-expressing fibroblasts could serve as promising therapeutic targets in colitis-associated CRC. In combination with previous work by others and us, our current findings highlight the context-dependent roles of COL1+ CAFs and COL6+ CAFs that might be variable according to the specific pathway activated.

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Heichler, C., Schmied, A., Enderle, K., Scheibe, K., Murawska, M., Schmid, B.,... Neufert, C. (2022). Targeting STAT3 Signaling in COL1+ Fibroblasts Controls Colitis-Associated Cancer in Mice. Cancers, 14(6).


Heichler, Christina, et al. "Targeting STAT3 Signaling in COL1+ Fibroblasts Controls Colitis-Associated Cancer in Mice." Cancers 14.6 (2022).

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