Inducible FGFR-1 Activation Leads to Irreversible Prostate Adenocarcinoma and an Epithelial-to-Mesenchymal Transition

Acevedo, Victor D.; Gangula, Rama; Freeman, Kevin W.; Li, Rile; Zhang, Yongyou; Wang, Fen; Ayala, Gustavo; Peterson, Leif E.; Ittmann, Michael; Spencer, David M.

doi:10.1016/j.ccr.2007.11.004

Cited by 268 publications

(248 citation statements)

References 45 publications

Supporting

Mentioning

232

Contrasting

Unclassified

Order By: Relevance

“…Murine models overexpressing key components of developmental signaling pathways alone or with other genetic alterations can drive a phenotype reminiscent of late-stage prostate cancer (19)(20)(21)(22). Although these studies provide evidence of a relationship between stem-like qualities and an aggressive phenotype, no studies to our knowledge have shown a molecular relationship between aggressive prostate cancer and uncultured stem-like cells from the human prostate.…”

Section: Significancementioning

confidence: 79%

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Smith

Sokolov

Uzunangelov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

178

172

View full text Add to dashboard Cite

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACSpurified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organconfined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells.RNA-seq | prostate cancer | stem cell signature | basal cell | neuroendocrine prostate cancer

show abstract

Section: Significancementioning

confidence: 79%

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Smith

Sokolov

Uzunangelov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

178

172

View full text Add to dashboard Cite

show abstract

“…The stromal expression and release of various FGFs are related to angiogenic and tumor-promoting effects. More specifi cally, studies in transgenic mice have linked FGFR1 activation and FGF8 epithelial overexpression to epithelial-mesenchymal transition and the induction of prostatic adenocarcinomas ( 47 ). A humanized monoclonal anti-FGF8 antibody and selective FGFR TKIs, such as AZ8010, …”

Section: Autocrine/paracrine Signalingmentioning

confidence: 99%

Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives

et al. 2013

View full text Add to dashboard Cite

The fi broblast growth factor/fi broblast growth factor receptor (FGF/FGFR) signaling pathway plays a fundamental role in many physiologic processes, including embryogenesis, adult tissue homeostasis, and wound healing, by orchestrating angiogenesis. Ligand-independent and ligand-dependent activation have been implicated in a broad range of human malignancies and promote cancer progression in tumors driven by FGF/FGFR oncogenic mutations or amplifi cations, tumor neoangiogenesis, and targeted treatment resistance, thereby supporting a strong rationale for anti-FGF/FGFR agent development. Efforts are being pursued to develop selective approaches for use against this pathway by optimizing the management of emerging, classspecifi c toxicity profi les and correctly designing clinical trials to address these different issues.Signifi cance: FGF/FGFR pathway deregulations are increasingly recognized across different human cancers. Understanding the mechanisms at the basis of these alterations and their multiple roles in cancer promotion and drug resistance is a fundamental step for further implementation of targeted therapies and research strategies. Cancer Discov;3(3);

show abstract

“…growth factor signaling). Among the growth factors known to induce EMT are transforming growth factor β (TGFβ) [3], hepatocyte growth factor (HGF) [4], members of the epidermal growth factor (EGF) family [5], insulin-like growth factor (IGF) [6], and fibroblast growth factor (FGF) [7,8]. Recently, also Notch signaling has been implicated in EMT in human breast cancer cells by activating the transcription factor Snail2 (Slug), a potent repressor of E-cadherin gene expression [9].…”

mentioning

confidence: 99%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,548

1,314

View full text Add to dashboard Cite

The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.

show abstract

Inducible FGFR-1 Activation Leads to Irreversible Prostate Adenocarcinoma and an Epithelial-to-Mesenchymal Transition

Cited by 268 publications

References 45 publications

A basal stem cell signature identifies aggressive prostate cancer phenotypes

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives

EMT, the cytoskeleton, and cancer cell invasion

Contact Info

Product

Resources

About