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Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population

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

ORGANISM(S): Mus musculus

PROVIDER: GSE154867 | GEO | 2020/11/17

REPOSITORIES: GEO

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Stromal SOX2 Upregulation Promotes Tumorigenesis through the Generation of a SFRP1/2-Expressing Cancer-Associated Fibroblast Population.

Project description:Cancer-associated fibroblasts (CAFs) promote tumor malignancy, but the precise transcriptional mechanisms regulating the acquisition of the CAF phenotype are not well understood. We show that the upregulation of SOX2 is central to this process, which is repressed by protein kinase Cζ (PKCζ). PKCζ deficiency activates the reprogramming of colonic fibroblasts to generate a predominant SOX2-dependent CAF population expressing the WNT regulator Sfrp2 as its top biomarker. SOX2 directly binds the Sfrp1/2 promoters, and the inactivation of Sox2 or Sfrp1/2 in CAFs impaired the induction of migration and invasion of colon cancer cells, as well as their tumorigenicity in vivo. Importantly, recurrence-free and overall survival of colorectal cancer (CRC) patients negatively correlates with stromal PKCζ levels. Also, SOX2 expression in the stroma is associated with CRC T invasion and worse prognosis of recurrence-free survival. Therefore, the PKCζ-SOX2 axis emerges as a critical step in the control of CAF pro-tumorigenic potential.

| S-EPMC7856011 | biostudies-literature

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [scRNA-seq]

Project description:Although how CAFs impact the tumor epithelium is being progressively unveiled, transcriptional processes of lineage plasticity in fibroblasts govern the acquisition of the CAF phenotype are much less understood. Here we show that the upregulation of SOX2 is a critical step in this process, which is negatively regulated by the atypical protein kinase (aPKC) PKCz. We demonstrate that the loss of PKCz is essential for the acquisition of the CAF phenotype and for the induction of the desmoplastic and more aggressive phenotype of intestinal tumors in a SOX2-dependent manner. Furthermore, we show here that the loss of PKCz drives the reprogramming of colon stromal fibroblasts into two different subpopulations that express either the Wnt regulators Sfrp1/2 or osteopontin, both ligands positively impinging into the mesenchymal and stem cell activation programs.

2020-11-17 | GSE154863 | GEO

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [ATAC-seq]

2020-11-17 | GSE154857 | GEO

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [Quant-seq]

2020-11-17 | GSE154852 | GEO

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [RNA-seq]

2020-11-17 | GSE154843 | GEO

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [scRNA-seq II]

2020-11-17 | GSE157697 | GEO

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population

Project description:Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population

| PRJNA647747 | ENA

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [Quant-seq]

Project description:Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [Quant-seq]

| PRJNA647763 | ENA

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [ATAC-seq]

Project description:Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [ATAC-seq]

| PRJNA647755 | ENA

Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [RNA-seq]

Project description:Stromal upregulation of SOX2 promotes tumorigenesis through the generation of a SFRP1/2-expressing cancer-associated fibroblast population [RNA-seq]

| PRJNA647771 | ENA

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