Hypoxia–reoxygenation increase invasiveness of PANC-1 cells through Rac1/MMP-2

Binker, Marcelo Gustavo; Binker-Cosen, Andres A.; Richards, Daniel A.; Gaisano, Herbert Y.; Cosen, Rodica; Cosen-Binker, Laura Iris

doi:10.1016/j.bbrc.2010.01.125

Cited by 32 publications

(26 citation statements)

References 27 publications

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“…The metastasis-suppressing role of this novel signaling pathway identified for CRMP4 in this study (Figure 5h) is in agreement with reports implicating that Akt inhibits Rac1 activity by direct phosphorylation of Rac1 [34,35]. It is known that Rac1 enhances prostate cancer invasion through activation of Rho GTPases and MMPs [30,32,33]. It appears that CRMP4-mediated suppression of meta stasis involves multiple signaling pathways.…”

Section: Discussionsupporting

confidence: 92%

Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase

2015

Oncotarget

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Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locusspecific CpG and subsequent histone modifications. These manipulations markedly altered expression of endogenous CRMP4, a metastasis suppressor gene. Remarkably, locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 cells abolished metastasis, whereas locus-specific CpG methylation of the promoter in nonmetastatic 22Rv1 cells induced metastasis. CRMP4-mediated metastasis suppression was found to require activation of Akt/Rac1 signaling and down-regulation of MMP-9 expression. This proof-of-concept study with dTALEs for locus-specific epigenomic manipulation validates the selected CpG methylation of CRMP4 gene as an independent biomarker for diagnosis and prognosis of prostate cancer metastasis and opens up a novel avenue for mechanistic research on cancer biology.

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Section: Discussionsupporting

confidence: 92%

Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase

2015

Oncotarget

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“…EGF activates Rac1 via both PI3K and Src pathways, and Rac1 enhances the invasion of cancer cells via the Rac1/NADPH/ROS/MMP-2 signaling pathways [76,78]. These studies also indicate that hypoxia reoxygenation enhances this signal pathway [79]. Other studies have found that high-mobility group AT-hook 1 (HMGA1), one architectural transcription factor overexpressed in pancreatic cancer, can be regulated by MMP-9 via the PI3K signaling pathway.…”

Section: Pi3k Signaling In Pancreatic Cancermentioning

confidence: 84%

“…Combining an IGF-IR inhibitor with gemcitabine resulted in additive anti-tumorigenic activity of pancreatic cancer both in vitro and in vivo [78]. Alternatively, treatment of gemcitabine-resistant pancreatic cancer cells with specific PI3K inhibitors (wortmannin and LY294002) enhanced gemcitabine-induced apoptosis in a concentration-dependent manner [79]. The nerve growth factor (NGF) tyrosine kinase receptor TrkA has been shown to be associated with malignant cellular behavior in a variety of human cancers.…”

Section: Pi3k Signaling In Pancreatic Cancermentioning

confidence: 99%

The Role of Phosphatidylinositol 3-Kinase Signaling Pathways in Pancreatic Cancer

et al. 2011

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“…The breakdown of the collagen barrier is expected due to the presence of various proteolytic enzymes excreted by PANC-1 cells including matrix metalloproteinase-2. 52 The staining/rinsing procedure also likely resulted in some mechanical breakdown of the weakened matrix. The observation of increased migration in the device with cells maintained under 1% oxygen is consistent with an extensive literature, suggesting that hypoxia generates a more aggressive phenotype 53,54 and was found in traditional transwell chamber assays for the PANC-1 cell line.…”

Section: F Cell Experiments and Growth Rate Comparisonmentioning

confidence: 99%

A microfluidic device to study cancer metastasis under chronic and intermittent hypoxia

et al. 2014

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Metastatic cancer cells must traverse a microenvironment ranging from extremely hypoxic, within the tumor, to highly oxygenated, within the host's vasculature. Tumor hypoxia can be further characterized by regions of both chronic and intermittent hypoxia. We present the design and characterization of a microfluidic device that can simultaneously mimic the oxygenation conditions observed within the tumor and model the cell migration and intravasation processes. This device can generate spatial oxygen gradients of chronic hypoxia and produce dynamically changing hypoxic microenvironments in long-term culture of cancer cells. V C 2014 AIP Publishing LLC. [http://dx

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Hypoxia–reoxygenation increase invasiveness of PANC-1 cells through Rac1/MMP-2

Cited by 32 publications

References 27 publications

Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase

Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase

The Role of Phosphatidylinositol 3-Kinase Signaling Pathways in Pancreatic Cancer

A microfluidic device to study cancer metastasis under chronic and intermittent hypoxia

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