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Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways

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

ORGANISM(S): Mus musculus

PROVIDER: GSE164971 | GEO | 2022/07/14

REPOSITORIES: GEO

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Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [ChIP-Seq]

Project description:Although a promotional role of the androgen receptor (AR) has been implicated in prostate tumorigenesis, the underlying mechanisms by which the AR, as a steroid-hormone receptor, induces prostatic oncogenesis still remain unknown. Conditional expression of the human AR transgene (hARtg) through Osr1 (old skipped related1) driven-Cre develops high-grade prostatic intraepithelial neoplasia (HGPIN) and adenocarcinomas in mice. Single-cell transcriptomic and genetic tracing analyses implicate the prostatic progenitor properties of prostatic Osr1-expressing cells through prostate development. Conditional expression of hARtg in Osr1-expressing basal epithelial cells elevates IGF1 signaling and initiates prostate oncogenesis and PIN formation. Aberrant IGF1 signaling further cumulates Wnt/b-catenin activation in atypical PIN cells to promote tumor development. Specific inhibition of Wnt signaling pathways significantly represses the growth of hARtg-positive prostate tumor cells in ex-vivo and xenograft models. These data elucidate a new and dynamic regulatory loop initiated by aberrant AR signaling altering IGF1 and Wnt signaling pathways in prostate oncogenesis and tumor development.

2022-07-14 | GSE164968 | GEO

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [RNA-Seq]

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Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [scRNA-Seq 1]

2022-07-14 | GSE164969 | GEO

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [scRNA-Seq 2]

2022-07-14 | GSE164970 | GEO

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways

Project description:Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways

| PRJNA692708 | ENA

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [RNA-Seq]

Project description:Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [RNA-Seq]

| PRJNA692709 | ENA

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [ChIP-Seq]

Project description:Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [ChIP-Seq]

| PRJNA692710 | ENA

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [scRNA-Seq 2]

Project description:Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [scRNA-Seq 2]

| PRJNA692711 | ENA

Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [scRNA-Seq 1]

Project description:Elucidating oncogenic effects of androgen signaling in prostate tumorigenesis through aberrant activation of IGF1 and WNT signaling pathways [scRNA-Seq 1]

| PRJNA692712 | ENA

Aberrant androgen action in prostatic progenitor cells induces oncogenesis and tumor development through IGF1 and Wnt axes.

Project description:Androgen/androgen receptor (AR) signaling pathways are essential for prostate tumorigenesis. However, the fundamental mechanisms underlying the AR functioning as a tumor promoter in inducing prostatic oncogenesis still remain elusive. Here, we demonstrate that a subpopulation of prostatic Osr1 (odd skipped-related 1)-lineage cells functions as tumor progenitors in prostate tumorigenesis. Single cell transcriptomic analyses reveal that aberrant AR activation in these cells elevates insulin-like growth factor 1 (IGF1) signaling pathways and initiates oncogenic transformation. Elevating IGF1 signaling further cumulates Wnt/β-catenin pathways in transformed cells to promote prostate tumor development. Correlations between altered androgen, IGF1, and Wnt/β-catenin signaling are also identified in human prostate cancer samples, uncovering a dynamic regulatory loop initiated by the AR through prostate cancer development. Co-inhibition of androgen and Wnt-signaling pathways significantly represses the growth of AR-positive tumor cells in both ex-vivo and in-vivo, implicating co-targeting therapeutic strategies for these pathways to treat advanced prostate cancer.

| S-EPMC9334353 | biostudies-literature

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