STAT5 and Prolactin Participate in a Positive Autocrine Feedback Loop That Promotes Angiogenesis

Yang, Xiaoqing; Meyer, Keith; Friedl, Andreas

doi:10.1074/jbc.m113.481119

Cited by 48 publications

(51 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mitogenic effect of PRL on endothelial cells is controversial. While some reports describe the induction of endothelial cell proliferation by PRL [27], we and other investigators have failed to observe this activity [26,28]. This apparent discrepancy may be due to different endothelial cells types studied or different functional states of the target cells.…”

Section: Stat5-induced Plf and Prl Promote Endothelial Cell Migrationcontrasting

confidence: 79%

“…The conditioned medium from CA-STAT5A but not from DN-STAT5A-expressing endothelial cells induces the phosphorylation of the PRLR and of ERK1/2. When PRL expression is silenced by RNAi, the CA-STAT5A conditioned medium failed to induce PRLR or ERK1/2 phosphorylation, demonstrating that PRL is bioactive and responsible for activation of the PRLR signaling pathway [26]. As expected from the mouse experiments, STAT5-induced PRL failed to stimulate human endothelial cell mitogenesis.…”

Section: Stat5-induced Plf and Prl Promote Endothelial Cell Migrationmentioning

confidence: 72%

“…The induction of PRL by CA-STAT5 could be the result of direct transcriptional regulation or it could be mediated by an indirect regulatory pathway. A NCBI Entrez Gene database analysis revealed multiple potential STAT5 binding sites within the PRL gene promoter region and ChIP confirmed STAT5 binding to the PRL promoter region in an activation-dependent manner [26]. Together, these observations in mice and humans point to an evolutionarily conserved mechanism where active STAT5 induces the secretion of a prolactin family member to mediate or synchronize proangiogenic events.…”

Section: Stat5 Induces Prolactin (Prl) Expression In Human Endotheliamentioning

confidence: 77%

“…Moreover, recombinant PRL can rescue endothelial cell tube formation in conditioned medium produced by cells in which PRL expression had been knocked down, implicating PRL as the active proangiogenic constituent. The proangiogenic effect of STAT5-induced PRL is not limited to human brain endothelial cells but is also seen in human umbilical cord endothelial cells (HUVEC) [26] (Yang, Friedl, unpublished data). Coexpression of PRL and STAT5 was detected in endothelial cells of some but not all human glioma tissue samples.…”

Section: Stat5-induced Plf and Prl Promote Endothelial Cell Migrationmentioning

confidence: 99%

“…Therefore, we investigated whether active STAT5 induces PRL secretion in human endothelial cells and whether PRL induces angiogenesis in vitro. Indeed, after STAT5 activation in human brain endothelial cells, elevated PRL protein secretion into the conditioned medium is detected, and PRL mRNA levels are increased, while growth hormone (GH) and placental lactogen (PL) remain unchanged [26]. The induction of PRL by CA-STAT5 could be the result of direct transcriptional regulation or it could be mediated by an indirect regulatory pathway.…”

Section: Stat5 Induces Prolactin (Prl) Expression In Human Endotheliamentioning

confidence: 99%

See 4 more Smart Citations

A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

Yang

Friedl

2014

Advances in Experimental Medicine and Biology

Self Cite

View full text Add to dashboard Cite

The signal transduction events that orchestrate cellular activities required for angiogenesis remain incompletely understood. We and others recently described that proangiogenic mediators such as fibroblast growth factors can activate members of the signal transducers and activators of transcription (STAT) family. STAT5 activation is necessary and sufficient to induce migration, invasion and tube formation of endothelial cells. STAT5 effects on endothelial cells require the secretion of the prolactin (PRL) family member proliferin-1 (PLF1) in mice and PRL in humans. In human endothelial cells, PRL activates the PRL receptor (PRLR) resulting in MAPK and STAT5 activation, thus closing a positive feedback loop. In vivo, endothelial cell-derived PRL is expected to combine with PRL of tumor cell and pituitary origin to raise the concentration of this polypeptide hormone in the tumor microenvironment. Thus, PRL may stimulate tumor angiogenesis via autocrine, paracrine, and endocrine pathways. The disruption of tumor angiogenesis by interfering with PRL signaling may offer an attractive target for therapeutic intervention.

show abstract

Section: Stat5-induced Plf and Prl Promote Endothelial Cell Migrationcontrasting

confidence: 79%

Section: Stat5-induced Plf and Prl Promote Endothelial Cell Migrationmentioning

confidence: 72%

Section: Stat5 Induces Prolactin (Prl) Expression In Human Endotheliamentioning

confidence: 77%

Section: Stat5-induced Plf and Prl Promote Endothelial Cell Migrationmentioning

confidence: 99%

Section: Stat5 Induces Prolactin (Prl) Expression In Human Endotheliamentioning

confidence: 99%

See 3 more Smart Citations

A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

Yang

Friedl

2014

Advances in Experimental Medicine and Biology

Self Cite

View full text Add to dashboard Cite

show abstract

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

et al. 2020

View full text Add to dashboard Cite

Many clinical trials for cancer precision medicine have yielded unsatisfactory results due to challenges such as drug resistance and low efficacy. Drug resistance is often caused by the complex compensatory regulation within the biomolecular network in a cancer cell. Recently, systems biological studies have modeled and simulated such complex networks to unravel the hidden mechanisms of drug resistance and identify promising new drug targets or combinatorial or sequential treatments for overcoming resistance to anticancer drugs. However, many of the identified targets or treatments present major difficulties for drug development and clinical application. Nanocarriers represent a path forward for developing therapies with these “undruggable” targets or those that require precise combinatorial or sequential application, for which conventional drug delivery mechanisms are unsuitable. Conversely, a challenge in nanomedicine has been low efficacy due to heterogeneity of cancers in patients. This problem can also be resolved through systems biological approaches by identifying personalized targets for individual patients or promoting the drug responses. Therefore, integration of systems biology and nanomaterial engineering will enable the clinical application of cancer precision medicine to overcome both drug resistance of conventional treatments and low efficacy of nanomedicine due to patient heterogeneity.

show abstract

The role of prolactin/vasoinhibins in cardiovascular diseases

Zhao

Gong

Shi³

et al. 2022

Anim Models and Exp Med

View full text Add to dashboard Cite

Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23‐kDa PRL (named full‐length PRL) and vasoinhibins (including 5.6–18 kDa fragments). Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization, including endothelial cell proliferation and migration, protease production, and apoptosis. However, their effects on vascular function and cardiovascular diseases are different or even contrary. In addition to the structure, secretion regulation, and signal transduction of PRL/vasoinhibins, this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

show abstract

STAT5 and Prolactin Participate in a Positive Autocrine Feedback Loop That Promotes Angiogenesis

Cited by 48 publications

References 63 publications

A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

The role of prolactin/vasoinhibins in cardiovascular diseases

Contact Info

Product

Resources

About