Formyl peptide receptors at the interface of inflammation, angiogenesis and tumor growth

Prevete, Nella; Liotti, Federica; Marone, Gianni; Melillo, Rosa Marina; Paulis, Amato de

doi:10.1016/j.phrs.2015.09.017

Cited by 90 publications

(103 citation statements)

References 70 publications

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“…AR directly influences PI3K/AKT signaling in cancer39. In addition, inflammation is also highly related to tumor angiogenesis40. NF-κB, the key player in inflammation, may also be involved in recruiting inflammatory immune cells to various tumors41 via PI3K/AKT signaling42.…”

Section: Discussionmentioning

confidence: 99%

Androgen receptor (AR) signaling promotes RCC progression via increased endothelial cell proliferation and recruitment by modulating AKT → NF-κB → CXCL5 signaling

Guan

Fan

et al. 2016

Sci Rep

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Androgen receptor (AR) signaling may promote renal cell carcinoma (RCC) progression via altered HIF-2α/VEGF signaling. However, it remains unclear whether AR signaling also promotes RCC progression by recruiting vascular endothelial cells (ECs), key players in the development of blood vessels. In our study, AR increased EC proliferation and recruitment to the tumor microenvironment and promoted RCC progression. Mechanistically, AR modulated cytokine CXCL5 expression by altering AKT → NF-κB signaling, and interruption of AKT → NF-κB → CXCL5 signaling using either specific inhibitors or siRNA suppressed AR-enhanced EC recruitment and AR-EC-promoted RCC progression. The results obtained using an in vivo mouse model and a human clinical sample survey confirmed the role of AR in promoting RCC progression through enhancement of EC proliferation and/or recruitment via altered AKT → NF-κB → CXCL5 signaling. Targeting this newly identified AR-induced AKT → NF-κB → CXCL5 pathway may facilitate the development of new therapies for slowing RCC progression.

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Section: Discussionmentioning

confidence: 99%

Androgen receptor (AR) signaling promotes RCC progression via increased endothelial cell proliferation and recruitment by modulating AKT → NF-κB → CXCL5 signaling

Guan

Fan

et al. 2016

Sci Rep

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“…The FPR-induced granule release results in a proteolytic cleavage of membrane-localized adhesion molecules and the liberation of proinflammatory matrix proteins and enzymes that can cause tissue degradation and killing of bacteria (17). Outside the immune system, FPRs have been implicated in various other functions, such as pain perception (40), wound healing (41), and olfactory pathogen sensing (16,29).…”

Section: Formyl Peptide Receptors Are G Protein-coupled Receptors Thamentioning

confidence: 99%

The sensing of bacteria: emerging principles for the detection of signal sequences by formyl peptide receptors

Bufe

Zufall

2016

Biomolecular Concepts

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The ability to detect specific chemical signatures released by bacteria and other microorganisms is a fundamental feature of immune defense against pathogens. There is increasing evidence that chemodetection of such microorganism-associated molecular patterns (MAMPs) occurs at many places in the body including specific sets of chemosensory neurons in the mammalian nose. Formyl peptide receptors (FPRs) are a unique family of G protein-coupled receptors (GPCRs) that can detect the presence of bacteria and function as chemotactic receptors. Here, we highlight the recent discovery of a vast family of natural FPR agonists, the bacterial signal peptides (or signal sequences), thus providing new insight into the molecular mechanisms of bacterial sensing by human and mouse FPRs. Signal peptides in bacteria are formylated, N-terminal protein signatures required for directing the transfer of proteins through the plasma membrane. After their cleavage and release, signal peptides are available for FPR detection and thus provide a previously unrecognized MAMP. With over 170 000 predicted sequences, bacterial signal peptides represent one of the largest families of GPCR ligands and one of the most complex classes of natural activators of the innate immune system. By recognizing a conserved three-dimensional peptide motif, FPRs employ an unusual detection mechanism that combines structural promiscuity with high specificity and sensitivity, thus solving the problem of detecting thousands of distinct sequences yet maintaining selectivity. How signal peptides are released by bacteria and sensed by GPCRs and how these processes shape the responses of other cells and whole organisms represents an important topic for future research.

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“…FPR1 is a G protein-coupled receptor that promotes growth, angiogenesis and invasion in glioblastoma tumor [61]. FPR1 as the other two FPRs play a pivotal role in inflammatory response, tissue repair, tumor growth, physiological and pathological angiogenesis [62]. PAPPA (pregnancy-associated plasma protein A) regulates mitotic progression through modulating the IGF1 signaling pathway [63].…”

Section: Resultsmentioning

confidence: 99%

Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma

et al. 2016

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Understanding the biology and molecular pathogenesis of ovarian epithelial cancer (EOC) is key to developing improved diagnostic and prognostic indicators and effective therapies. Although research has traditionally focused on the hypothesis that high-grade serous carcinoma (HGSC) arises from the ovarian surface epithelium (OSE), recent studies suggest that additional sites of origin exist and a substantial proportion of cases may arise from precursor lesions located in the Fallopian tubal epithelium (FTE). In FTE cells, the transcription factor PAX8 is a marker of the secretory cell lineage and its expression is retained in 96% of EOC. We have recently reported that PAX8 is involved in the tumorigenic phenotype of ovarian cancer cells. In this study, to uncover genes and pathways downstream of PAX8 involved in ovarian carcinoma we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by means of a silencing approach followed by an RNA-seq analysis. Interestingly, we highlighted the involvement of pathways like WNT signaling, epithelial-mesenchymal transition, p53 and apoptosis. We believe that our analysis has led to the identification of candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma.

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Formyl peptide receptors at the interface of inflammation, angiogenesis and tumor growth

Cited by 90 publications

References 70 publications

Androgen receptor (AR) signaling promotes RCC progression via increased endothelial cell proliferation and recruitment by modulating AKT → NF-κB → CXCL5 signaling

Androgen receptor (AR) signaling promotes RCC progression via increased endothelial cell proliferation and recruitment by modulating AKT → NF-κB → CXCL5 signaling

The sensing of bacteria: emerging principles for the detection of signal sequences by formyl peptide receptors

Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma

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