Targeting STAT3 Signaling in COL1+ Fibroblasts Controls Colitis-Associated Cancer in Mice Article Swipe
Christina Heichler
,
Anabel Schmied
,
Karin Enderle
,
Kristina Scheibe
,
Marta Murawska
,
Benjamin Schmid
,
Maximilian J. Waldner
,
Markus F. Neurath
,
Clemens Neufert
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3390/cancers14061472
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/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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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cancers14061472
- https://www.mdpi.com/2072-6694/14/6/1472/pdf?version=1647232781
- OA Status
- gold
- Cited By
- 8
- References
- 64
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4220655055
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4220655055Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/cancers14061472Digital Object Identifier
- Title
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Targeting STAT3 Signaling in COL1+ Fibroblasts Controls Colitis-Associated Cancer in MiceWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-03-14Full publication date if available
- Authors
-
Christina Heichler, Anabel Schmied, Karin Enderle, Kristina Scheibe, Marta Murawska, Benjamin Schmid, Maximilian J. Waldner, Markus F. Neurath, Clemens NeufertList of authors in order
- Landing page
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https://doi.org/10.3390/cancers14061472Publisher landing page
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https://www.mdpi.com/2072-6694/14/6/1472/pdf?version=1647232781Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://www.mdpi.com/2072-6694/14/6/1472/pdf?version=1647232781Direct OA link when available
- Concepts
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Cancer-Associated Fibroblasts, Cancer research, Colorectal cancer, Tumor microenvironment, Cancer, STAT3, Inflammation, Medicine, Context (archaeology), Signal transduction, Chemistry, Immunology, Biology, Cell biology, Internal medicine, PaleontologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2023: 7Per-year citation counts (last 5 years)
- References (count)
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64Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.options. | 11 |
| abstract_inverted_index.previous | 211 |
| abstract_inverted_index.promotes | 144 |
| abstract_inverted_index.reported | 54 |
| abstract_inverted_index.reporter | 173 |
| abstract_inverted_index.specific | 237 |
| abstract_inverted_index.strategy | 88 |
| abstract_inverted_index.variable | 233 |
| abstract_inverted_index.according | 234 |
| abstract_inverted_index.addition, | 151 |
| abstract_inverted_index.different | 111 |
| abstract_inverted_index.evaluated | 109 |
| abstract_inverted_index.functions | 42 |
| abstract_inverted_index.highlight | 220 |
| abstract_inverted_index.including | 113 |
| abstract_inverted_index.indicates | 177 |
| abstract_inverted_index.promising | 202 |
| abstract_inverted_index.readouts, | 112 |
| abstract_inverted_index.represent | 69 |
| abstract_inverted_index.signaling | 183 |
| abstract_inverted_index.treatment | 10 |
| abstract_inverted_index.Colorectal | 0 |
| abstract_inverted_index.activated. | 239 |
| abstract_inverted_index.activation | 82, 131, 141, 193 |
| abstract_inverted_index.colorectal | 170 |
| abstract_inverted_index.importance | 13 |
| abstract_inverted_index.inhibition | 128 |
| abstract_inverted_index.microscopy | 120 |
| abstract_inverted_index.population | 73 |
| abstract_inverted_index.signaling. | 60 |
| abstract_inverted_index.suggesting | 187 |
| abstract_inverted_index.understood | 39 |
| abstract_inverted_index.combination | 209 |
| abstract_inverted_index.conditional | 91, 95 |
| abstract_inverted_index.demonstrate | 125 |
| abstract_inverted_index.development | 107, 146 |
| abstract_inverted_index.fibroblasts | 16, 134, 198 |
| abstract_inverted_index.recognized. | 28 |
| abstract_inverted_index.therapeutic | 203 |
| abstract_inverted_index.constitutive | 140 |
| abstract_inverted_index.contribution | 180 |
| abstract_inverted_index.distribution | 158 |
| abstract_inverted_index.fibroblasts, | 67 |
| abstract_inverted_index.increasingly | 27 |
| abstract_inverted_index.NFκB-related | 59 |
| abstract_inverted_index.characterizes | 154 |
| abstract_inverted_index.co-expression | 156 |
| abstract_inverted_index.methodologies, | 116 |
| abstract_inverted_index.gain-of-function | 92 |
| abstract_inverted_index.loss-of-function | 96 |
| abstract_inverted_index.microenvironment | 21 |
| abstract_inverted_index.cancer-associated | 15 |
| abstract_inverted_index.context-dependent | 222 |
| abstract_inverted_index.colitis-associated | 104, 206 |
| abstract_inverted_index.collagen-expressing | 51, 197 |
| abstract_inverted_index.inflammation-driven | 148 |
| abstract_inverted_index.inflammation-associated | 169 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 91 |
| corresponding_author_ids | https://openalex.org/A5015760121 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I181369854, https://openalex.org/I4210088053 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.800000011920929 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.74881402 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |