Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway

Graziani, Irene; Eliasz, Sandra; Marco, Melissa A. De; Chen, Yuanbin; Pass, Harvey I.; May, Richard M. De; Strack, Peter R.; Miele, Lucio; Bocchetta, Maurizio

doi:10.1158/0008-5472.can-08-0969

Cited by 112 publications

(99 citation statements)

References 39 publications

(52 reference statements)

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“…It has been reported that cross-talk between Notch signaling and PI3K/Akt pathway could influence tumor progression (Kunnimalaiyaan and Chen, 2007;Meurette et al, 2009). Notch1 activation was reported to suppress the expression of PTEN, a key molecule in PI3K/Akt pathway, in T-ALL and mesothelioma cell (Palomero Graziani et al, 2008). There was also a report concerning the involvement of Notch1 in PTEN upregulation in human 293 cells (Whelan et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

Ding

et al. 2011

Oncogene

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Section: Resultsmentioning

confidence: 99%

Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

Ding

et al. 2011

Oncogene

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“…Similarly, Notch2 has been shown to play a key role in the establishment and survival of the Sus cell population of the OE (60), but Notch1 does not. With respect to disease processes, it is known that Notch1 and Notch2 play opposite roles in oncogenesis and have been used as opposing cancer prognostication factors (61)(62)(63). Additionally, Notch1 and Notch2 play different roles in diabetic nephropathy (64).…”

Section: Discussionmentioning

confidence: 99%

Notch1 maintains dormancy of olfactory horizontal basal cells, a reserve neural stem cell

Herrick

Lin

Peterson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The remarkable capacity of the adult olfactory epithelium (OE) to regenerate fully both neurosensory and nonneuronal cell types after severe epithelial injury depends on life-long persistence of two stem cell populations: the horizontal basal cells (HBCs), which are quiescent and held in reserve, and mitotically active globose basal cells. It has recently been demonstrated that down-regulation of the ΔN form of the transcription factor p63 is both necessary and sufficient to release HBCs from dormancy. However, the mechanisms by which p63 is down-regulated after acute OE injury remain unknown. To identify the cellular source of potential signaling mechanisms, we assessed HBC activation after neuron-only and sustentacular cell death. We found that ablation of sustentacular cells is sufficient for HBC activation to multipotency. By expression analysis, nextgeneration sequencing, and immunohistochemical examination, down-regulation of Notch pathway signaling is coincident with HBC activation. Therefore, using HBC-specific conditional knockout of Notch receptors and overexpression of N1ICD, we show that Notch signaling maintains p63 levels and HBC dormancy, in contrast to its suppression of p63 expression in other tissues. Additionally, Notch1, but not Notch2, is required to maintain HBC dormancy after selective neuronal degeneration. Taken together, our data indicate that the activation of HBCs observed after tissue injury or sustentacular cell ablation is caused by the reduction/elimination of Notch signaling on HBCs; elimination of Jagged1 expressed by sustentacular cells may be the ligand responsible.Notch | olfactory epithelium | reserve stem cell | trp63

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“…Moreover, alterations of Notch signaling that function in tumor initiation, progression, angiogenesis and metastasis have been found to be mediated through the activation of several important downstream pathways. Until now, b-catenin, 17 AKT, 32,33,38 Pin1, 39 Snail, 22 MMP9 19 and HES1 36 have been reported to either function as the downstream targets or be associated with Notch signaling in cancers. Notch signaling induces EMT Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Notch1‐Snail1‐E‐cadherin pathway in metastatic hepatocellular carcinoma

Wang

Zhang

Lui

et al. 2011

Intl Journal of Cancer

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Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the reestablishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis.Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and is ranked second amongst all cancer deaths in Hong Kong. HCC is correlated with an increased likelihood of vascular invasion, metastasis and recurrence (even after surgical resection), leading to poor prognosis. 1 Metastasis, both intrahepatic and extrahepatic, is of particular concern and occurs in more than half of HCC cases. 2 The incidence of high grade HCC that metastasize to distant sites is high. 2 However, the detailed mechanisms of metastasis are yet to be revealed.The process that converts adherent epithelial cells into migratory cells to invade the extracellular matrix is called the epithelial-mesenchymal transition (EMT). This process plays fundamental roles in tissue and organ formation during embryonic development and in wound healing and tissue repair during adult life. 3,4 However, the abnormal activation of EMT programs can be disadvantageous to cancer patients. 3 EMT can allow carcinoma cells to acquire mesenchymal cell gene expression profiles and properties, 5 leading to the transformation of the cells from being coherent and displaying apicobasal polarity to become nonpolarized cells that can move through the extracellular media. This transformation enables the spread of tumor cells to distant sites. 6,7 Although EMT is considered to be the first step in the metastatic progression of migratory cancer cells, EMT has not been confirmed to exist in vivo. 3...

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Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway

Abstract: Malignant mesothelioma (MM) is a cancer of the lining of the lungs, heart, and intestine and is known to respond poorly to chemotherapy. Here we show

Cited by 112 publications

References 39 publications

Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

Notch1 maintains dormancy of olfactory horizontal basal cells, a reserve neural stem cell

Notch1‐Snail1‐E‐cadherin pathway in metastatic hepatocellular carcinoma

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