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Cancer associated fibroblasts play an important role in prostate cancer progression

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

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE213670 | GEO | 2023/06/22

REPOSITORIES: GEO

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Cancer associated fibroblasts play an important role in prostate cancer progression [ATAC-Seq]

Project description:To understand the cell types changes in prostate cancer progression, we carried out scRNA-seq of prostates from different kinds of genetic mouse model. After that, we found fibroblasts were changed obviously during prostate cancer progression. To confirm the function of the fibroblasts, LNCap was used to cocultured with all kinds of fibroblasts in control or ADT condition. To find out the key enviroment factors induced firoblast changing, RNA-seq, ATAC-seq and ChIP-seq of fibroblast in different treatment were taken. And finally, ADT, TGF-β1, and sox4 were confirmed as contributors of the stroma cell changes, which provided new strategies for prostate cancer treatment. scRNA-seq were used to find out the cell lines diverisity of prostate cancer progressiom. RNA-seq of LNCap cocultured with different fibroblasts were taken to identify the pathway fibroblasts induced. RNA-seq, ATAC-seq and ChIP-seq of fibroblasts were carried out to find out the reason of fibroblast changes.

2023-06-22 | GSE213665 | GEO

Cancer associated fibroblasts play an important role in prostate cancer progression [RNA-Seq]

2023-06-22 | GSE213663 | GEO

Cancer associated fibroblasts play an important role in prostate cancer progression [ChIP-Seq]

2023-06-22 | GSE213664 | GEO

Cancer associated fibroblasts play an important role in prostate cancer progression

Project description:Cancer associated fibroblasts play an important role in prostate cancer progression

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Cancer associated fibroblasts play an important role in prostate cancer progression [RNA-Seq]

Project description:Cancer associated fibroblasts play an important role in prostate cancer progression [RNA-Seq]

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Cancer associated fibroblasts play an important role in prostate cancer progression [ATAC-Seq]

Project description:Cancer associated fibroblasts play an important role in prostate cancer progression [ATAC-Seq]

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Cancer associated fibroblasts play an important role in prostate cancer progression [ChIP-Seq]

Project description:Cancer associated fibroblasts play an important role in prostate cancer progression [ChIP-Seq]

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Invadopodia play a role in prostate cancer progression.

Project description:BackgroundInvadopodia, actin-rich structures that release metallo-proteases at the interface with extra-cellular matrix, in a punctate manner are thought to be important drivers of tumour invasion. Invadopodia formation has been observed in-vitro and in-vivo in numerous metastatic cell lines derived from multiple tumour types. However, prostate cancer cell lines have not been routinely reported to generate invadopodia and the few instances have always required external stimulation.MethodsIn this study, the invasive potential of primary prostate adenocarcinoma cell lines, which have never been fully characterised before, was investigated both in-vitro invadopodia assays and in-vivo zebrafish dissemination assay. Subsequently, circulating tumour cells from prostate cancer patients were isolated and tested in the invadopodia assay.ResultsRetention of E-cadherin and N-cadherin expression indicated a transitional state of EMT progression, consistent with the idea of partial EMT that has been frequently observed in aggressive prostate cancer. All cell lines tested were capable of spontaneous invadopodia formation and possess a significant degradative ability in-vitro under basal conditions. These cell lines were invasive in-vivo and produced visible metastasis in the zebrafish dissemination assay. Importantly we have proceeded to demonstrate that circulating tumour cells isolated from prostate cancer patients exhibit invadopodia-like structures and degrade matrix with visible puncta. This work supports a role for invadopodia activity as one of the mechanisms of dissemination employed by prostate cancer cells.ConclusionThe combination of studies presented here provide clear evidence that invadopodia activity can play a role in prostate cancer progression.

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YAP1 plays a key role of the conversion of normal fibroblasts into cancer-associated fibroblasts that contribute to prostate cancer progression.

Project description:BackgroundCancer-associated fibroblasts (CAFs) are an important part of the tumour microenvironment, and their functions are of great concern. This series of experiments aimed to explore how Yes-associated protein 1 (YAP1) regulates the function of stromal cells and how the normal fibroblasts (NFs) convert into CAFs in prostate cancer (PCa).MethodsThe effects of conditioned media from different fibroblasts on the proliferation and invasion of epithelial cells TrampC1 were examined. We then analysed the interaction between the YAP1/TEAD1 protein complex and SRC, as well as the regulatory function of the downstream cytoskeletal proteins and actins. A transplanted tumour model was used to explore the function of YAP1 in regulating tumour growth through stromal cells. The relationship between the expression of YAP1 in tumour stromal cells and the clinical characteristics of PCa patients was analysed.ResultsThe expression level of YAP1 was significantly upregulated in PCa stromal cells. After the expression level of YAP1 was increased, NF was transformed into CAF, enhancing the proliferation and invasion ability of epithelial cells. The YAP1/TEAD1 protein complex had the capability to influence downstream cytoskeletal proteins by regulating SRC transcription; therefore, it converts NF to CAF, and CAF can significantly promote tumour growth and metastasis. The high expression of YAP1 in the tumour stromal cells suggested a poor tumour stage and prognosis in PCa patients.ConclusionYAP1 can convert NFs into CAFs in the tumour microenvironment of PCa, thus promoting the development and metastasis of PCa. Silencing YAP1 in tumour stromal cells can effectively inhibit tumour growth.

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IL6/JAK/STAT3-mediated crosstalk between cancer associated fibroblasts and epithelial cells promotes lineage plasticity and prostate cancer progression.

Project description:This SuperSeries is composed of the SubSeries listed below.

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