What question did this study set out to answer?

Investigate the functional heterogeneity of cancer-associated fibroblasts in colorectal cancer and identify specific molecular mechanisms driving tumor progression and poor prognosis.

April 1, 2025Cell ReportsOpen Access

THBS2-producing matrix CAFs promote colorectal cancer progression and link to poor prognosis via the CD47-MAPK axis

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Investigate the functional heterogeneity of cancer-associated fibroblasts in colorectal cancer and identify specific molecular mechanisms driving tumor progression and poor prognosis.
Analyzed colorectal cancer tissue profiles using single-cell RNA sequencing, spatial transcriptomics, and multiplex immunohistochemistry.
Evaluated downstream signaling and validated tumor-promoting mechanisms using fibroblast-specific THBS2 knockout mice, patient-derived organoids, and xenograft models.
Identified a matrix cancer-associated fibroblast subtype that secretes THBS2, colocalizes with tumor cells, and correlates with advanced disease stages and poor survival.
Demonstrated that fibroblast-derived THBS2 binds to CD47 on colorectal cancer cells to activate MAPK/ERK5 signaling and accelerate tumor growth.
Identified transcription factor CREB3L1 as the key driver mediating the transformation of normal fibroblasts into THBS2-secreting matrix fibroblasts.

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Implication

Translational study reveals THBS2-secreting matrix fibroblasts promote tumor progression in colorectal cancer via CD47-MAPK signaling, highlighting potential therapeutic targets.

Cite This Study

Liu et al. (2025) studied this question.

synapsesocial.com/papers/6a85ac499df929a58fada856 https://doi.org/10.1016/j.celrep.2025.115555

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Implication

Translational study reveals THBS2-secreting matrix fibroblasts promote tumor progression in colorectal cancer via CD47-MAPK signaling, highlighting potential therapeutic targets.

THBS2-producing matrix CAFs promote colorectal cancer progression and link to poor prognosis via the CD47-MAPK axis

Key Points

Discussion

Implication

Cite This Study

THBS2-producing matrix CAFs promote colorectal cancer progression and link to poor prognosis via the CD47-MAPK axis

Key Points

Discussion

Implication

Cite This Study

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