Dataset Information

Notch1 Signaling Contributes to Hypoxia-induced High Expression of Integrin ?1 in Keratinocyte Migration.

ABSTRACT: Oxygen tension is an important micro-environmental factor that affects epidermal development and function. After injury, high oxygen consumption and vascular injury result in partial hypoxia. However, whether hypoxia benefits or hurts wound healing remains controversial. In this study, a tissue oxygen tension monitor was used to detect the spatial and temporal distribution of oxygen in burn wounds. In vitro, we demonstrate that hypoxia promoted the expression of integrin ?1 and the migration of keratinocytes. Furthermore, hypoxia-induced migration was slowed by Notch1 ligands and a siRNA against ITGB1 (integrin ?1). Our findings suggest that integrin ?1 may be an oxygen-sensitive molecule that promotes keratinocyte migration during wound healing and that Notch1 signaling is involved in this process.

SUBMITTER: Tang D

PROVIDER: S-EPMC5339698 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Notch1 Signaling Contributes to Hypoxia-induced High Expression of Integrin β1 in Keratinocyte Migration.

Tang Di D Yan Tiantian T Zhang Junhui J Jiang Xupin X Zhang Dongxia D Huang Yuesheng Y

Scientific reports 20170307

Oxygen tension is an important micro-environmental factor that affects epidermal development and function. After injury, high oxygen consumption and vascular injury result in partial hypoxia. However, whether hypoxia benefits or hurts wound healing remains controversial. In this study, a tissue oxygen tension monitor was used to detect the spatial and temporal distribution of oxygen in burn wounds. In vitro, we demonstrate that hypoxia promoted the expression of integrin β1 and the migration of ...[more]

PMID: 28266574

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Project description:BackgroundProfound chemoresistance remains an intractable obstacle in pancreatic cancer treatment. Pancreatic cancer stem cells (CSCs) and the ubiquitous hypoxic niche have been proposed to account for drug resistance. However, the mechanism involved requires further exploration. This study investigated whether the hypoxic niche enhances gemcitabine-induced stemness and acquired resistance in pancreatic cancer cells by activating the AKT/Notch1 signaling cascade. The therapeutic effects of blockading this signaling cascade on gemcitabine-enriched CSCs were also investigated.MethodsThe expression levels of CSC-associated markers Bmi1 and Sox2 as well as those of proteins involved in AKT/Notch1 signaling were measured by Western blot analysis. The expression level of the pancreatic CSC marker CD24 was measured by flow cytometry. Change in gemcitabine sensitivity was evaluated by the MTT assay. The ability of sphere formation was tested by the sphere-forming assay in stem cell medium. The ability of migration and invasion was detected by the transwell migration/invasion assay. A mouse xenograft model of pancreatic cancer was established to determine the effect of Notch1 inhibition on the killing effect of gemcitabine in vivo. The ability of metastasis was investigated by an in vivo lung metastasis assay.ResultsGemcitabine promoted pancreatic cancer cell stemness and associated malignant phenotypes such as enhanced migration, invasion, metastasis, and chemoresistance. The AKT/Notch1 signaling cascade was activated after gemcitabine treatment and mediated this process. Blockading this pathway enhanced the killing effect of gemcitabine in vivo. However, supplementation with hypoxia treatment synergistically enhanced the AKT/Notch1 signaling pathway and collaboratively promoted gemcitabine-induced stemness.ConclusionsThese findings demonstrate a novel mechanism of acquired gemcitabine resistance in pancreatic cancer cells through induction of stemness, which was mediated by the activation of AKT/Notch1 signaling and synergistically aggravated by the ubiquitous hypoxic niche. Our results might provide new insights for identifying potential targets for reversing chemoresistance in patients with pancreatic cancer.

Dataset Information

Notch1 Signaling Contributes to Hypoxia-induced High Expression of Integrin ?1 in Keratinocyte Migration.

Publications

Notch1 Signaling Contributes to Hypoxia-induced High Expression of Integrin β1 in Keratinocyte Migration.

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