Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

Sasaki, Takeshi; Yoshikawa, Yuzo; Kageyama, Takumi; Sugino, Yusuke; Kato, Manabu; Masui, Satoru; Nishikawa, Kouhei; Inoue, Takahiro

doi:10.1002/pros.24468

Cited by 3 publications

(1 citation statement)

References 40 publications

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“…The results of RT-qPCR assays ( Figure 4 C) indicated that only LNCaP and 22Rv1 cells express measurable ARFL and ARv7 mRNA instead of PZ-HPV-7, CA-HPV-10, PC-3, and DU145 cells; moreover, 22Rv1 cells express endogenously abundant ARv7. These results are in agreement with previous reports [ 43 , 47 , 48 ]. Both ectopic overexpressed-ARv7 22Rv1 and PC-3 cells induced NDRG1 expression compared to mock-transfected 22Rv1 and PC-3 cells, respectively; in addition, the ectopic overexpression of ARv7 induced PSA expression in 22Rv1 cells under androgen ablation conditions ( Figure 5 ).…”

Section: Discussionsupporting

confidence: 94%

Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells

Chang

Chen

Sung

et al. 2023

IJMS

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The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

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Section: Discussionsupporting

confidence: 94%

Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells

Chang

Chen

Sung

et al. 2023

IJMS

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The Mechanism by Which Hedgehog Interacting Protein (HHIP) in Cancer-Associated Fibroblasts Regulate the Secretion of Inflammatory Factors Through the JAK1/STAT3 Pathway Affecting Prostate Cancer Stemness

Wo,

Shi,

Shi

et al. 2024

JIR

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Prostate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation

Hönscheid,

Baretton,

Puhr

et al. 2024

IJMS

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Cancer-associated fibroblast (CAF)s in the tumour microenvironment (TME) modulate the extracellular matrix, interact with cancer cells, and facilitate communication with infiltrating leukocytes, significantly contributing to cancer progression and therapeutic response. In prostate cancer (PCa), CAFs promote malignancy through metabolic rewiring, cancer stem cell regulation, and therapy resistance. Pre-clinical studies indicate that targeting amino acid metabolism, particularly glutamine (Gln) metabolism, reduces cancer proliferation and stemness. However, most studies lack the context of CAF–cancer interaction, focusing on monocultures. This study assesses the influence of CAFs on PCa growth by manipulating Gln metabolism using colour-labelled PCa cell lines (red) and fibroblast (green) in a co-culture system to evaluate CAFs’ effects on PCa cell proliferation and clonogenic potential. CAFs increased the proliferation of hormone-sensitive LNCaP cells, whereas the castration-resistant C4-2 cells were unaffected. However, clonogenic growth increased in both cell lines. Gln deprivation and GLS1 inhibition experiments revealed that the increased growth rate of LNCAP cells was associated with increased dependence on Gln, which was confirmed by proteomic analyses. Tissue analysis of PCa patients revealed elevated GLS1 levels in both the PCa epithelium and stroma, suggesting that GLS1 is a therapeutic target. Moreover, the median overall survival analysis of GLS1 expression in the PCa epithelium and stroma identified a “high-risk” patient group that may benefit from GLS1-targeted therapies. Therefore, GLS1 targeting appears promising in castration-resistant PCa patients with high GLS1 epithelium and low GLS1 stromal expression.

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Prostate fibroblasts enhance androgen receptor splice variant 7 expression in prostate cancer cells

Cited by 3 publications

References 40 publications

Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells

Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells

The Mechanism by Which Hedgehog Interacting Protein (HHIP) in Cancer-Associated Fibroblasts Regulate the Secretion of Inflammatory Factors Through the JAK1/STAT3 Pathway Affecting Prostate Cancer Stemness

Prostate Cancer’s Silent Partners: Fibroblasts and Their Influence on Glutamine Metabolism Manipulation

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