Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity

Jia, Dongyu; Zhou, Zhicheng; Kwon, Oh-Joon; Zhang, Li; Wei, Xing; Zhang, Yiqun; Yi, Mingyang; Roudier, Martine P.; Regier, Mary C.; Dumpit, Ruth; Nelson, Peter S.; Headley, Mark B.; True, Lawrence D.; Lin, Daniel W.; Morrissey, Colm; Creighton, Chad J.; Li, Xin

doi:10.1038/s41467-022-34665-z

Cited by 15 publications

(5 citation statements)

References 58 publications

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“…Again, FOXF2 (Forkhead Box F2) in the prostate stroma reduced the iCAF phenotypic ratio, induced its transformation to myCAF, and downregulated CXCL5, thereby reducing immunosuppressive myeloid cells and enhancing T cell cytotoxicity. Further, increasing the content of Foxf2 sensitized PCa to ICB therapy [ 413 ]. The gene set variation analysis by Zhai, X., and colleagues indicated that pathways like PPAR, GnRH, and mTOR are significantly correlated with PCa and might become targeted landmarks [ 414 ].…”

Section: Background Knowledge Of Cafsmentioning

confidence: 99%

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Zhang,

Yue,

Chen

et al. 2023

Mol Cancer

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Despite centuries since the discovery and study of cancer, cancer is still a lethal and intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as a pivotal component of the tumor microenvironment. The versatility and sophisticated mechanisms of CAFs in facilitating cancer progression have been elucidated extensively, including promoting cancer angiogenesis and metastasis, inducing drug resistance, reshaping the extracellular matrix, and developing an immunosuppressive microenvironment. Owing to their robust tumor-promoting function, CAFs are considered a promising target for oncotherapy. However, CAFs are a highly heterogeneous group of cells. Some subpopulations exert an inhibitory role in tumor growth, which implies that CAF-targeting approaches must be more precise and individualized. This review comprehensively summarize the origin, phenotypical, and functional heterogeneity of CAFs. More importantly, we underscore advances in strategies and clinical trials to target CAF in various cancers, and we also summarize progressions of CAF in cancer immunotherapy.

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Section: Background Knowledge Of Cafsmentioning

confidence: 99%

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Zhang,

Yue,

Chen

et al. 2023

Mol Cancer

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“…CAFs, as a crucial component of the tumor microenvironment, plays a critical role in PCa progression [25]. [27]. In our current study, we uncovered that the hypoxic TME stimulates CAFs to release exosomes rich in miR-500a-3p, which subsequently in uence PCa phenotypes by targeting speci c mRNA.…”

Section: Discussionmentioning

confidence: 59%

Cancer-associated fibroblasts exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment

Niu,

Liu,

Lin

et al. 2023

Preprint

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Metastasis is the main cause of deaths in prostate cancer (PCa). However, the mechanisms of PCa metastasis remain unknown. In this study, severe hypoxia was identified in primary lesions of metastasis PCa (mPCa). The exosomes secreted by cancer-associated fibroblasts (CAFs) significantly promoted PCa metastasis in vitro and in vivo. miRNA sequencing analysis and reverse transcription quantitative PCR (RT-qPCR) experiments indicated miR-500a-3p was significantly increased in CAFs exosomes under hypoxia. RT-qPCR, western blotting, and dual luciferase reporter assays were used to identify FBXW7 was a target of miR-500a-3p. Using immunohistochemistry, we found a decrease in FBXW7 expression with PCa progression, while there was an increase in HSF1 expression. After FXBW7 plasmid transfection, the metastasis ability was suppressed and HSF1 expression significantly decreased in PCa cells. These data indicated that CAFs exosomes promote PCa metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment. Targeting hypoxia or exosomal miR-500a-3pmay provide a potential treatment strategy for the management of PCa.

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“…In prostate cancer, HIC2 protein expression was shown to be increased in tumors compared with benign hyperplasia and normal tissue with a Gleason score greater than 7 and grade 3 ( 52 ). Collagen Type III Alpha 1 Chain (COL3A1) is a protein that is found in most soft connective tissues along with type I collagen ( 53, 54 ). It is involved in the regulation of cortical development, and it is the major ligand of ADGRG1 in the developing brain.…”

Section: Resultsmentioning

confidence: 99%

Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts

Sychev,

Day,

Bergom

et al. 2024

Molecular Cancer Research

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Resistance to androgen deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform to emergent aggressive variant prostate cancer (AVPC) which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflects and retains key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, that included six different PDX tumors for each group in biological replicates and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa. Implications: Overall, our study highlights the importance of protein-based identification when compared to RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.

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Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity

Cited by 15 publications

References 58 publications

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Cancer-associated fibroblasts exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment

Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts

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