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Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE169725 | GEO | 2021/12/31

REPOSITORIES: GEO

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Prrx1 is a Master Transcription Factor of myofibroblastic Cancer-Associated Fibroblasts [Murine_Fibroblast_ChIP_seq]

Project description:Although cancer associated fibroblasts (CAF) play a critical role in cancer progression, their identities are still unknown. Because cells’ own identity is determined by core regulatory circuit (CRC) comprising master transcription factors (TFs), it is critical to find CAF’s master TF. Therefore, we attempt to find master TF of CAF through the extensive screening of single cell RNA-seq database of cancer tissues, and discovered Prrx1, master regulator of embryonic mesenchymal cells, as candidate for master TF of CAF. Prrx1 was abundantly expressed in CAFs with significant correlation with unfavorable clinical outcomes. Furthermore, Prrx1 in fibroblasts dramatically enhanced tumor progression and metastasis in fibroblast-specific Prrx1 inducible mice. On the other hand, tumor formation was severely inhibited in conditional Prrx1 knock-down mice. Finally, we confirmed that Prrx1 is a master TF of CAF and normal fibroblast executing wound healing program using ChIP-SEQ, CRC modeling, and in vivo validation. Furthermore we also revealed that targeting Prrx1 in fibroblast alone induced complete remission of chemotherapy-resistant cancer in preclinical mouse experiments.

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