STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis
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View abstract on PubMed
Summary
This summary is machine-generated.Signal transducer and activator of transcription 3 (STAT3) activation in cancer-associated fibroblasts (CAFs) drives colorectal cancer (CRC) development. Blocking proangiogenic signaling in CAFs significantly reduced tumor growth, highlighting STAT3 as a therapeutic target in CRC.
Area Of Science
- Oncology
- Cancer Biology
- Tumor Microenvironment
Background
- Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment, influencing tumor growth and progression.
- The specific role of CAFs in colorectal cancer (CRC) development remains incompletely understood, necessitating further investigation into their functional mechanisms.
Purpose Of The Study
- To investigate the role of signal transducer and activator of transcription 3 (STAT3) activation in CAFs during colorectal cancer development.
- To explore the functional consequences of STAT3 signaling in fibroblasts on tumorigenesis and identify potential therapeutic targets in CRC.
Main Methods
- Quantification of phosphorylated STAT3 (pSTAT3) in CAFs from human colon cancer tissues using tissue microarrays (TMAs) and digital pathology.
- Utilized genetically modified murine models for loss-of-function and gain-of-function experiments to assess STAT3 signaling in fibroblasts.
- Employed whole genome RNA-sequencing for comparative gene expression profiling of fibroblast subpopulations and advanced imaging technologies.
Main Results
- Increased stromal pSTAT3 expression in CAFs negatively correlated with patient survival in colon cancer.
- STAT3 activation in fibroblasts was found to be critical for driving colorectal tumorigenesis in vivo.
- STAT3 activation in fibroblasts regulated transcriptional patterns associated with angiogenesis, and blockade of proangiogenic signaling reduced tumor growth.
Conclusions
- STAT3 activation in cancer-associated fibroblasts plays a critical role in the development of colorectal cancer.
- Targeting STAT3 signaling and its downstream proangiogenic effects presents a potential therapeutic strategy for CRC.
Keywords:
colorectal cancer
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