Identification and Optimization of Small Molecules That Restore E-Cadherin Expression and Reduce Invasion in Colorectal Carcinoma Cells

Stoops, Sydney L.; Pearson, A. Scott; Waterson, Alex G.; Days, Emily; Farmer, Chris; Brady, Suzanne C.; Weaver, C. David; Beauchamp, R. Daniel; Lindsley, Craig W.

doi:10.1021/cb100305h

Cited by 34 publications

(33 citation statements)

References 26 publications

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“…CRC cells present either mutations of the E-cadherin gene, proteolytic degradation of E-cadherin, insulin growth factor 1-promoted internalization of E-cadherin or disarrangement of E-cadherin and β-catenin connections [67,68] . Notably, intact cadherin-catenin complexes support the normal function of intercellular adhesion and guarantee stable "adherens junctions" and an unimpaired Wnt signalling pathway (the latter being a complex protein network controlling signal transduction) [69] .…”

Section: Transition Of Epithelial Cells In the Large Intestinementioning

confidence: 99%

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Paschos

Majeed

Bird

2014

WJG

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Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. Paschos KA, Majeed AW, Bird NC. Natural history of hepatic metastases from colorectal cancer -pathobiological pathways with clinical significance.

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Section: Transition Of Epithelial Cells In the Large Intestinementioning

confidence: 99%

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Paschos

Majeed

Bird

2014

WJG

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“…Significant therapeutic interest in the reversal of EMT is highlighted by the exploration of synthetic molecular compounds to restore E-cadherin expression. [101][102][103] The controlled induction of MET could have benefit for the reversal of several pathophysiological states where there is a dysregulated EMT.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer

2011

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“…Small molecules that can restore E-cadherin expression in SW620 cells have been shown to reduce invasion [26] .…”

Section: Discussionmentioning

confidence: 99%

Overexpression Of Prostate Apoptosis Response Protein-4 In Colon Cancer Cells Can Inhibit Metastasis By Upregulating E-cadherin Expression

Nguyen¹,

Kline²,

Caballero³

et al. 2015

JCRC

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Colon cancer has a five-year survival of 64.7%, and about 50,000 people are expected to die from colon cancer this year. Patients with metastatic colorectal cancer have a significantly worse prognosis, a 12.9% five -year survival. This emphasizes the need for strategies to inhibit the growth and metastases of colorectal cancer. Prostate apoptosis response protein 4 (Par-4) is a pro-apoptotic protein that has been shown to mediate apoptosis in response to stimuli, such as chemotherapeutics and radiation. Recombinant Par-4 protein has been shown to reduce the occurrence of Lewis lung carcinoma metastases in-vivo; however, the mechanism by which Par-4 can inhibit metastasis has not been elucidated. In this study, human colon cancer cell lines -SW480 and SW620 -were transfected with Par-4 plasmid or anti-Par-4 shRNA, and the effect on metastasis was examined. Par-4 overexpression inhibited cell migration and invasion, while Par-4 knockdown promoted it. Moreover, the morphology of SW620 cells was altered when Par-4 levels were increased. The change was characteristic of a mesenchymal-to-epithelial transition (MET) in these cells. MET can be induced by upregulation of E-cadherin expression, and RT-PCR and Western blot analyses showed that E-cadherin mRNA and protein levels, respectively, were increased in the Par-4 overexpressing cells concomitant with a decrease in vimentin. The results of this study demonstrate the potential of Par-4 in colon cancer therapy, not only in primary tumors but also in metastatic cells.

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Identification and Optimization of Small Molecules That Restore E-Cadherin Expression and Reduce Invasion in Colorectal Carcinoma Cells

Cited by 34 publications

References 26 publications

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer

Overexpression Of Prostate Apoptosis Response Protein-4 In Colon Cancer Cells Can Inhibit Metastasis By Upregulating E-cadherin Expression

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