Src kinase regulates metalloproteinase-9 secretion induced by type IV collagen in MCF-7 human breast cancer cells

Cortés‐Reynosa, Pedro; Robledo, Teresa; Macı́as-Silva, Marina; Wu, Shaofeng; Salazar, Eduardo Pérez

doi:10.1016/j.matbio.2007.11.003

Cited by 64 publications

(61 citation statements)

References 84 publications

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“…Gli1, a transcription factor activated in the Hh pathway, significantly enhanced tumor growth and metastases of other cancers through the activation of ERK1/2 [42,45] . Overexpression of MMP-9 is also a key factor for tumor invasion and metastasis [47,48,55] . Moreover, the Hh signaling pathway may enhance migration and invasion of cancer cells by increasing the expression of MMP-9 [49,50] .…”

Section: Discussionmentioning

confidence: 99%

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Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Lü

Zhao

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the role of Hedgehog (Hh) signaling pathway in the invasion and metastasis of human hepatocellular carcinoma (HCC). Methods: Eighty six HCC tissues samples and HCC cell line Bel-7402 were examined. The protein expression of sonic hedgehog (Shh), nuclear glioma-associated oncogene-1 (Gli1), MMP-9 and p-ERK1/2 in HCC was analyzed using immunohistochemistry and Western blot analysis. Boyden chamber assay and wound-healing assay were used to quantify the invasion and metastasis of Bel-7402 cells. Results: In 86 HCC tissue samples, the positive ratio of Shh and nucleus Gli1 was 67.44% (58/86) and 60.47% (52/86), respectively; the expression of nucleus Gli1 was correlated with the tumor pathological grade (P=0.034), and with the ability of the tumor to invade and metastasize (P=0.001); the expression of nucleus Gli1 was also correlated with p-ERK1/2 (P=0.031) and with MMP-9 (P=0.034). Neither Shh, nor nucleus Gli1 was observed in normal liver tissue. KAAD-cyclopamine (KAAD-cyc), a specific inhibitor of the Hh pathway, at the concentrations of 1 and 4 μmol/L inhibited the invasion and migration of Bel-7402 cells and decreased the expression of Gli1 in nucleus and MMP-9, p-ERK1/2 proteins in Bel-7402 cells. On the other hand, Shh, a ligand of the Hh pathway, at the concentration of 0.5 μg/mL produced opposite effects. The MAPK pathway inhibitors U0126 and PD98059 at the concentrations of 5 and 10 μmol/L inhibited invasion and metastasis of Bel-7402 cells induced by Shh, and decreased the expression of p-ERK1/2 and MMP-9. However, U0126 and PD98059 had no effect on the expression of Gli1. Conclusion: Hh signaling pathway mediates invasion and metastasis of human HCC by up-regulating the protein expression of MMP-9 via ERK pathway.

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Section: Discussionmentioning

confidence: 99%

“…Matrix metalloproteinase-9 (MMP-9 or gelatinase-B) is mostly associated with tumor migration, invasion and metastasis for various human cancers [10,47,48] . The Hh signaling pathway up-regulates cell migration and invasion in human gliomas and in pancreatic cancer by increasing the expressions of MMP-9 [49,50] .…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Lü

Zhao

et al. 2012

Acta Pharmacol Sin

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“…2). Trihydoxystilbene resveratrol (11) and its triacetate (12) and tetrahydroxystilbene piceatannol (14), and its tetraacetate (15) and dimer (16) reduced the pro-MMP-9 production at a concentration of 10 or 25 μM (Fig. 3).…”

Section: Effects Of Various Stilbenes On Vegf and Pro-mmp-9 Productiomentioning

confidence: 96%

“…Moreover, the MMP proteolytic system may also modulate tumor angiogenesis by modulating the release of biologically active vascular endothelial growth factor (VEGF). (8,9) Among MMPs, there are a number of reports that MMP-9 production plays an important role in invasion, metastasis of cancer cells, (10)(11)(12)(13)(14)(15)(16) and tumor growth. (17)(18)(19)(20)(21)(22)(23)(24) Tumor angiogenesis involves the directional sprouting of new vessels toward a solid tumor.…”

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confidence: 99%

Antitumor activities of synthetic and natural stilbenes through antiangiogenic action

Kimura¹,

Sumiyoshi

2008

Cancer Science

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We reported that the antitumor and antimetastatic actions of resveratrol might be due to the inhibition of tumor-induced angiogenesis. To search for anticancer agents with stronger activity than resveratrol, we examined the antiangiogenic effects of 21 synthetic and/or natural stilbenes. Among these 21 stilbenes, 2,3-, 3,4-, and 4,4′-dihydroxystilbene inhibited the pro-matrix metalloproteinase (pro-MMP)-9 production in colon 26 cells at 5-25 mM, vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) migration at 10 and 25 mM, and VEGFinduced angiogenesis at 5-50 mM. Resvertarol inhibited the pro-MMP-9 production and VEGF-induced angiogenesis at 25 or 50 mM. Thus, the inhibition of pro-MMP-9 production in colon 26 cells and VEGF-induced angiogenesis by three dihydroxystilbenes were greater than those of resveratrol. The three dihydroxystilbenes (8 mg/kg, intraperitoneal injection) inhibited the tumor-induced neovascularization in colon 26-packed chamber-bearing mice and the tumor growth in colon 26-bearing mice. Furthermore, the three dihydroxystilbenes inhibited VEGF-induced VEGFR-2 phosphorylation. On the other hand, the three dihydroxystilbenes had no effect on VEGFR-1 and-2 expression, and VEGF-induced VEGFR-1 phosphorylation in HUVECs. These findings suggest that the inhibition of tumor-induced neovascularization by these three dihydroxystilbenes may be due (1) They stimulate cancer cell growth, migration, invasion, angiogenesis, and metastasis. (2) When MMPs are secreted from tumor cells, the invasion of tumor cells is facilitated by increased intravasation and extravasation through the degradation of the ECM and basement membranes.

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“…For example, cell surface activation of an MMP can occur when gelatinase A (MMP-2) is brought into contact with a membrane-associated MMP, MT-1 MMP [10,11]. MMP-2 and MMP-9 (gelatinase B) have their greatest enzymatic activities against type IV collagen, which is the main constituent of the basement membrane [12,13].…”

Section: Integrinsmentioning

confidence: 99%

Membrane and membrane‐associated proteins involved in the aggressive phenotype displayed by highly invasive cancer cells

2008

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Invasion, the penetration of tumour cells into adjacent tissues, is a fundamental characteristic of malignant carcinomas and a first step in the metastatic process. The molecular mechanisms involved in tumour cell invasion are complex, but over the last couple of decades the knowledge base has grown quite considerably and many proteins with important roles in invasion have been identified and characterised. Benign tumours typically are encapsulated, which inhibits their ability to behave in a malignant manner, meaning these tumours do not grow in a location-limited less aggressive manner, do not invade surrounding tissues and do not metastasise. The ability of malignant tumours to invade and metastasise is the major cause of death for cancer patients. A greater insight into the molecular basis of cancer invasion and metastasis will lead to the development of novel therapies and specific panels of biomarkers for use in the treatment and diagnosis/monitoring in many types of metastatic cancer.

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Src kinase regulates metalloproteinase-9 secretion induced by type IV collagen in MCF-7 human breast cancer cells

Cited by 64 publications

References 84 publications

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

Antitumor activities of synthetic and natural stilbenes through antiangiogenic action

Membrane and membrane‐associated proteins involved in the aggressive phenotype displayed by highly invasive cancer cells

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