Adherens junction-dependent PI3K/Akt activation induces resistance to genotoxin-induced cell death in differentiated intestinal epithelial cells

Chae, Boah; Yang, Kyoung Min; Kim, Tae Il

doi:10.1016/j.bbrc.2008.11.120

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…These Wndings are in agreement with those previously observed showing that PI3K inhibition through overexpression of PTEN or Wortmannin treatment of HT-29 and Caco-2 cells resulted in increased alkaline phosphatase and sucrose-isomaltase activities, suggesting a regulatory eVect of this pathway on intestinal cell diVerentiation (Wang et al 2001). On the contrary, other studies using Caco-2 cells showed that E-cadherin assembly leads to a rapid and remarkable activation of Akt, suggesting that PI3K promotes AJ assembly, leading to Akt activation and enterocyte diVerentiation (Laprise et al 2002;Chae et al 2009). It is possible that the contradictory Wndings are due to the use of diVerent cell lines.…”

Section: Pi3k Inhibition Interferes With Akt and Gsk-3 Activities Andmentioning

confidence: 57%

PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells

Araújo

Vidal

Souza

et al. 2010

J Cancer Res Clin Oncol

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Section: Pi3k Inhibition Interferes With Akt and Gsk-3 Activities Andmentioning

confidence: 57%

PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells

Araújo

Vidal

Souza

et al. 2010

J Cancer Res Clin Oncol

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“…The cadherin family of genes is associated with CCN3, which has been found to have prognostic value in Osteosarcoma [48]. CDH13 and CHD9 are also part of the adherens junction biological process; and adherens-dependent PI3K/AKT activation is known to induce resistance to genotoxin-induced cell death in intestinal epithelial cells [49].…”

Section: Discussionmentioning

confidence: 99%

Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients

et al. 2019

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Background Osteosarcoma is the most common malignant bone tumor in children. Survival remains poor among histologically poor responders, and there is a need to identify them at diagnosis to avoid delivering ineffective therapy. Genetic variation contributes to a wide range of response and toxicity related to chemotherapy. The aim of this study is to use sequencing of blood cells to identify germline haplotypes strongly associated with drug resistance in osteosarcoma patients. Methods We used sequencing data from two patient datasets, from Inova Hospital and the NCI TARGET. We explored the effect of mutation hotspots, in the form of haplotypes, associated with relapse outcome. We then mapped the single nucleotide polymorphisms (SNPs) in these haplotypes to genes and pathways. We also performed a targeted analysis of mutations in Drug Metabolizing Enzymes and Transporter (DMET) genes associated with tumor necrosis and survival. Results We found intronic and intergenic hotspot regions from 26 genes common to both the TARGET and INOVA datasets significantly associated with relapse outcome. Among significant results were mutations in genes belonging to AKR enzyme family, cell-cell adhesion biological process and the PI3K pathways; as well as variants in SLC22 family associated with both tumor necrosis and overall survival. The SNPs from our results were confirmed using Sanger sequencing. Our results included known as well as novel SNPs and haplotypes in genes associated with drug resistance. Conclusion We show that combining next generation sequencing data from multiple datasets and defined clinical data can better identify relevant pathway associations and clinically actionable variants, as well as provide insights into drug response mechanisms. Electronic supplementary material The online version of this article (10.1186/s12885-019-5474-y) contains supplementary material, which is available to authorized users.

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“…pAkt is also considered to be a marker of differentiation and its expression has been shown to increase in differentiated Caco-2 cells. 170 Its inhibition is known to affect differentiation of olfactory bulb stem cells. 171 Signaling by p-Akt is also known to prevent the cancer phenotype of some colorectal cancer cells.…”

Section: Expression Of P-aktmentioning

confidence: 99%

“…170 We examined the levels of E-cadherin in cell lysates from 3, 4, 7 or 14 days old cells. We observed that the expression of E-cadherin was not significantly different on various days (Figure 4.7B).…”

Section: Expression Of E-cadherinmentioning

confidence: 99%

Role of Extracellular Signal-Regulated Kinase (ERK) in Regulation of Intestinal Epithelial Tight Junctions

Aggarwal¹

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Adherens junction-dependent PI3K/Akt activation induces resistance to genotoxin-induced cell death in differentiated intestinal epithelial cells

Cited by 7 publications

References 19 publications

PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells

PI3K/Akt and GSK-3β prevents in a differential fashion the malignant phenotype of colorectal cancer cells

Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients

Role of Extracellular Signal-Regulated Kinase (ERK) in Regulation of Intestinal Epithelial Tight Junctions

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