Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway

Choi, Young‐Ae; Lim, Hyung-Kyu; Kim, Jae-Ryong; Lee, ChuHee; Kim, Young-Jo; Kang, Shin‐Sung; Baek, Suk‐Hwan

doi:10.1074/jbc.m314235200

Cited by 47 publications

(38 citation statements)

References 43 publications

(38 reference statements)

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“…These data suggested that CD9 modulated MMP-2 production of blastocysts cultured on FN via the PI3K signaling pathway. This result is in agreement with studies of MMP-2 in NIH3T3 and MDA-MB-231 cells (Sugiura & Berditchevski 1999, Choi et al 2004.…”

Section: Discussionsupporting

confidence: 82%

Tetraspanin CD9 regulates invasion during mouse embryo implantation

Liu¹,

Cao²,

Yang³

et al. 2006

Journal of Molecular Endocrinology

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The expression of tetraspanin CD9 was found on blastocysts in mice and endometrium epithelial cells in human and bovine. However, it remains unknown how CD9 is involved in the precise dialogue between embryo and uterus during early pregnancy. This study was designed to investigate the functional roles of CD9 in the embryo implantation with monoclonal antibody against CD9 protein (anti-CD9 mAb) and antisense oligonucleotide against CD9 gene (AS-CD9). Our results showed that intrauterine injection of anti-CD9 mAb on day 4 of pregnancy significantly increased the number of embryos implanted (7·24±0·39 versus 4·04±0·38). In vitro, anti-CD9 mAb or AS-CD9 significantly enhanced embryo-outgrowth ability on the monolayer of uterus epithelial cells in a dose-dependent manner. However, the attachment of blastocysts to epithelial cells was unaffected. Furthermore, we found that anti-CD9 mAb or AS-CD9 stimulated matrix metalloproteinase 2 (MMP-2) production of blastocysts on Fibronectin. LY294002, a specific inhibitor of phosphoinositide 3-kinase, was able to counteract the effect of anti-CD9 mAb and AS-CD9 on outgrowth ability and production of MMP-2. Our results indicated that CD9 played a role of inhibiting embryo implantation. CD9 was able to impair embryo invasion and the production of MMP-2 through the phosphoinositide 3-kinase signaling pathway.

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Section: Discussionsupporting

confidence: 82%

Tetraspanin CD9 regulates invasion during mouse embryo implantation

Liu¹,

Cao²,

Yang³

et al. 2006

Journal of Molecular Endocrinology

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“…Many reports, including our study, have shown that PI3K/ Akt pathway is critically involved in MMP-2 expression (19,(42)(43)(44). However, none of these studies revealed the relationship between PI3K/Akt signaling pathway and AP-2 activation.…”

Section: Discussionmentioning

confidence: 47%

Nerve Growth Factor Induces Endothelial Cell Invasion and Cord Formation by Promoting Matrix Metalloproteinase-2 Expression through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway and AP-2 Transcription Factor

Park

Kwak

Lee

et al. 2007

Journal of Biological Chemistry

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Nerve growth factor (NGF) is a well characterized neurotrophic agonist in the nervous system that triggers angiogenesis. In this study, we investigated the signaling mechanisms involved in NGF-induced angiogenesis. NGF stimulated endothelial cell invasion and cord formation on Matrigel in vitro but had marginal effect on proliferation and migration of these cells. NGF stimulated matrix metalloproteinase (MMP)-2 mRNA expression and protein secretion in human umbilical vein endothelial cells. Using synthetic and endogenous inhibitors of MMP-2 and MMP-2 small interfering RNA suppressed NGF-induced invasion and cord formation. We demonstrated that NGF-induced MMP-2 secretion, invasion, and cord formation are regulated via activation of the NGF receptor, TrkA, phosphatidylinositol 3-kinase (PI3K), and Akt using various pharmacological inhibitors. Specifically, NGF enhanced TrkA phosphorylation, PI3K activity, and Akt phosphorylation. Introduction of NGF-neutralizing antibodies, dominant-negative Akt, or wild-type PTEN effectively inhibited NGF-induced MMP-2 secretion and cord formation. Deletion and site-directed mutagenesis analysis of the MMP-2 promoter demonstrated that the AP-2-binding site is critical for NGF-induced MMP-2 promoter activity. NGF increased the DNA binding activity of AP-2, which was suppressed by inhibitors of TrkA and PI3K. Furthermore, transfection of AP-2 small interfering RNA effectively blocked NGFinduced MMP-2 secretion and cord formation. Finally, NGF promoted neovessel formation in Matrigel plugs in vivo, which was significantly inhibited by K252a and LY294002, but it failed to promote angiogenesis using MMP-2 knock-out mice. Our data collectively suggest that NGF stimulates endothelial cell invasion and cord formation by augmenting MMP-2 via the PI3K/Akt signaling pathway and AP-2 transcription factor, which may be responsible for triggering angiogenesis.

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“…Numerous reports have demonstrated that MMP-2 expression is critically mediated by MAPK members 13,15) and PI3K/Akt pathway. 23,33,34) MAPK and PI3K/Akt pathways also play an important role in endothelial cell viability, migration, and tube formation by specific stimuli. [13][14][15]25,35,36) Therefore, we examined the effect of a-chaconine on the activities of MAPK and PI3K/Akt signaling pathways.…”

Section: Fig 3 Effect Of A-chaconine On Chemotaxis and Invasion Of mentioning

confidence: 99%

.ALPHA.-Chaconine Inhibits Angiogenesis in Vitro by Reducing Matrix Metalloproteinase-2

Chen

Shih

et al. 2010

Biological & Pharmaceutical Bulletin

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Glycoalkaloids are the biologically active secondary metabolites found in many plants, such as potatoes. Glycoalkaloids are produced in leaves, roots, tubers and sprouts of the potato plant, and are involved in host plant resistance to bacteria, fungi, viruses, and insects. 1) Several reports have showed that glycoalkaloids suppress the growth of cancer cells in human skin, liver, prostate, breast and colon. 2-4) aChaconine, a trisaccharide glycoalkaloid, is the main steroidal glycoalkaloid in potato (Solanum tuberosum). 1) Recent studies demonstrated that a-chaconine inhibited the growth of human colon (HT29), liver (HepG2), cervical (HeLa), lymphoma (U937), and stomach (AGS and KATO III) cancer cells. 3,5) a-Chaconine also induced apoptosis of human colon cancer cells through the inhibition of extracellular signal regulating kinase (ERK) phosphorylation and activation of caspase-3. 6) In addition, a-chaconine inhibited migration and invasion of human lung adenocarcinoma A549 cells by reducing matrix metalloproteinase (MMP)-2 and MMP-9 activities through the suppression of phosphatidylinositide-3 kinase/ Akt/nuclear factor kappa B (PI3K/Akt/NF-kB) signaling pathway. 7) Therefore, a-chaconine may possess the potential for cancer chemotherapeutic action.Angiogenesis, a process of new blood vessel formation from a pre-existing microvascular network, plays important roles in many physiological functions including wound healing, embryonic development, and the normal menstrual cycle. Angiogenesis is also involved in pathological conditions, such as ischemia, atherosclerosis, arthritis and carcinogenesis. 8) During tumor development, newly generated vessels are necessary for supplying sufficient oxygen and nutrients to the growing tumor mass, and facilitating the metastatic spreading. 8,9) The process of angiogenesis includes proliferation, migration, invasion, as well as tube formation of endothelial cells. The process of angiogenesis is promoted by expressing and secreting various proteases that can degrade most extracellular matrix (ECM) components. 10) MMPs, a family of Zn-dependent endopeptidases, are the major proteases in angiogenesis and are closely correlated with invasive and metastatic potentials of cancer cells. 11) Several MMPs, such as MMP-2 and MT1-MMP, are produced by endothelial cells and contribute to the process of angiogenesis. 12) As well as MMPs, the mitogen-activated protein kinases family members (MAPK) are also known to mediate angiogenesis. MAPK family members participate in numerous signaling cascades that play important regulatory roles in cell growth, apoptosis, differentiation, and angiogenesis. The diverse MAPK members are activated in response to various extracellular stimuli and have distinct downstream targets, thus stimulating endothelial cell proliferation and protease production, and acting as positive mediators of angiogenesis. [13][14][15] Angiogenesis is also regulated by PI3K/Akt signaling pathway, which has been implicated in a number of cellular functions including cell survi...

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Group IB Secretory Phospholipase A2 Promotes Matrix Metalloproteinase-2-mediated Cell Migration via the Phosphatidylinositol 3-Kinase and Akt Pathway

Cited by 47 publications

References 43 publications

Tetraspanin CD9 regulates invasion during mouse embryo implantation

Tetraspanin CD9 regulates invasion during mouse embryo implantation

Nerve Growth Factor Induces Endothelial Cell Invasion and Cord Formation by Promoting Matrix Metalloproteinase-2 Expression through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway and AP-2 Transcription Factor

.ALPHA.-Chaconine Inhibits Angiogenesis in Vitro by Reducing Matrix Metalloproteinase-2

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