16-kDa Prolactin Inhibits Endothelial Cell Migration by Down-Regulating the Ras-Tiam1-Rac1-Pak1 Signaling Pathway

Lee, Sok Hyong; Kunz, Jeannette; Lin, Sue Hwa; Yu-Lee, Li-Yuan

doi:10.1158/0008-5472.can-07-0986

Cited by 60 publications

(44 citation statements)

References 53 publications

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“…Similarly, we found that Wnt protein is able to induce PAK1 activation in HEK293T cells and endogenous PAK1 activity is partially required for full b-catenin accumulation in both HEK293T and mouse L-cells upon Wnt stimulation. In colon cancer cells, signaling from K-Ras/Rac1 (Lee et al, 2007;Wang et al, 2010b), IGF (Sun et al, 2009) or EGF (Galisteo et al, 1996;Lu et al, 1997) pathways all may induce PAK1 activation, which maintains the high phosphorylation state of b-catenin S675.…”

Section: Discussionmentioning

confidence: 99%

A Rac1/PAK1 cascade controls β-catenin activation in colon cancer cells

et al. 2011

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P21-activated kinase 1 (PAK1) is associated with colon cancer progression and metastasis, whereas the molecular mechanism remains elusive. Here, we show that downregulation of PAK1 in colon cancer cells reduces total b-catenin level, as well as cell proliferation. Mechanistically, PAK1 directly phosphorylates b-catenin proteins at Ser675 site and this leads to more stable and transcriptional active b-catenin. Corroborating these results, PAK1 is required for full Wnt signaling, and superactivation of b-catenin is achieved by simultaneous knockdown of adenomatous polyposis coli protein and activation of PAK1. Moreover, we show that Rac1 functions upstream of PAK1 in colon cancer cells and contributes to b-catenin phosphorylation and accumulation. We conclude that a Rac1/PAK1 cascade controls b-catenin S675 phosphorylation and full activation in colon cancer cells. Supporting this conclusion, overexpression of PAK1 is observed in 70% of colon cancer samples and is correlated with massive b-catenin accumulation.

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Section: Discussionmentioning

confidence: 99%

A Rac1/PAK1 cascade controls β-catenin activation in colon cancer cells

et al. 2011

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“…Rac1 is required for activation of hypoxia inducible factor 1 (Hirota et al, 2001). Rac1 is also necessary for the induction of VEGFR-2 in vascular endothelial cells (Meissner et al, 2009) and is necessary for endothelial cell migration (Lee et al, 2007). VEGF activates Rac1 via vav-2 (Garrett et al, 2007) and activation of Rac1 is involved in the hypoxia-induced production of angiogenesis-promoting factors (Xue et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronic Acid Promotes Angiogenesis by Inducing RHAMM-TGFβ Receptor Interaction via CD44-PKCδ

Park

Kim

et al. 2012

Molecules and Cells

142

101

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“…This assay was performed as recommended by earlier research (24,50). Briefly, each well of the 96-well plates was precoated with 50 l of Matrigel (BD Biosciences, Bedford, MA) and allowed to polymerize for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells

Guo

Sang

Yin

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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-Acute glucose fluctuations (AGF) often cause high mortality among critically ill patients, but the mechanisms induced by AGF are not clear. Recent studies suggest that endothelial dysfunction is a key factor that leads to high mortality among critically ill patients. Our goal is to evaluate the phenomenon and mechanisms of endothelial dysfunction induced by AGF. In this study, the functions of human umbilical vein endothelial cells (HUVECs) were compared after treatment with sustained high glucose (SHG), AGF in two groups (AGF1 fluctuations between 5 and 16 mM and AGF2 fluctuations between 5 and 25 mM), and normal glucose levels as a control group (CTR). The medium of the groups was changed every 4 h. The influence of AGF on wound healing was also tested on C57BL/6 mice. The results show that cell proliferation, angiogenesis, and migration functions were injured in the SHG and both AGF groups. AGF2 group shows the worse condition in vitro. In vivo, the wound healing was delayed after the AGF treatment. Furthermore, the markers of apoptosis and autophagy were analyzed. We observed that the autophagy changed in all treatment groups, but apoptosis showed no change. To get to know the mechanism of dysfunction and autophagy, we performed the microRNA chip assay and real-time PCR and found miR-1273g-3p remarkably changed in AGF2 group. After the mimic and inhibitor of miR-1273g-3p were transfected during the AGF2 treatment, we found that the dysfunction and autophagy were partially enhanced by miR-1273g-3p mimic and reversed by miR-1273g-3p inhibitor in AGF2 group. Thus, we conclude that AGF can induce more dysfunction and autophagy, and miR-1273g-3p is also an important factor that leads to the injury. glucose fluctuations; endothelial dysfunction; wound healing; autophagy; miR-1273g-3pINCREASING GLYCEMIC VARIABILITY can greatly increase the risk of mortality among critically ill patients. Several previous studies suggest that the variability in glucose levels over time is an important determinant of mortality among critically ill patients (21,22,58). Alternatively, recent evidence shows that glucose fluctuations may influence the development of diabetic complications(4, 47) and may produce more serious injury in organ functions than sustained high blood glucose. Krinsley and Preiser (20) reported that if a blood glucose range of 70 -140 mg/dl is maintained for Ͼ80% of the time, the chances of survival of nondiabetic critically ill adults will be greatly increased. Organ injury induced by glucose toxicity is commonly observed in both intensive care units and endocrine departments. The damage is also observed in in vitro cell culture and animal studies. Therefore, some authors have proposed that "glycemic variability" is a new therapeutic challenge in diabetes and the critical care setting (7).The mechanism of the production of glucose fluctuations is variable in several studies (35)(36)(37)(38)(39)57) in both preclinical and clinical research studies. However, this is not appropriate for the critically ill patient...

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16-kDa Prolactin Inhibits Endothelial Cell Migration by Down-Regulating the Ras-Tiam1-Rac1-Pak1 Signaling Pathway

Cited by 60 publications

References 53 publications

A Rac1/PAK1 cascade controls β-catenin activation in colon cancer cells

A Rac1/PAK1 cascade controls β-catenin activation in colon cancer cells

Hyaluronic Acid Promotes Angiogenesis by Inducing RHAMM-TGFβ Receptor Interaction via CD44-PKCδ

miR-1273g-3p participates in acute glucose fluctuation-induced autophagy, dysfunction, and proliferation attenuation in human umbilical vein endothelial cells

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