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

Xy, Ding; Ding, Jin; Wu, Keng‐Liang; Wen, Wang; C, Liu; Hx, Yan; Chen, C; Wang, S; Tang, Hua; Ck, Gao; Ln, Guo; Cao, Deliang; Z, Li; Feng, Gong Kan; Hy, Wang; Xu, Zeping

doi:10.1038/onc.2011.467

Cited by 34 publications

(27 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a study demonstrated that endothelial cells, through augmented expression of Delta-4, prevent the proliferation of NSCLC cells by activating Notch signaling. In this specific model, most of the anti-oncogenic functions were mediated by Notch-4 through elevation of Notch-1 expression, hence enhancing PTEN expression 43. In conclusion, there are data supporting anti-oncogenic role of Notch signaling in the lung epithelia that may contradict the previous summary of Notch-3 involvement in lung carcinogenesis.…”

Section: The Controversial Role Of Notch-1 In Nsclccontrasting

confidence: 54%

Non-small-cell lung carcinoma: role of the Notch signaling pathway

Barse¹,

Bocchetta²

2015

LCTT

View full text Add to dashboard Cite

Notch signaling plays a pivotal role during embryogenesis. It regulates three fundamental processes: lateral inhibition, boundary formation, and lineage specification. During post-natal life, Notch receptors and ligands control critical cell fate decisions both in compartments that are undergoing differentiation and in pluripotent progenitor cells. First recognized as a potent oncogene in certain lymphoblastic leukemias and mesothelium-derived tissue, the role of Notch signaling in epithelial, solid tumors has been far more controversial. The overall consequence of Notch signaling and which form of the Notch receptor drives malignancy in humans is deeply debated. Most likely, this is due to the high degree of context-dependent effects of Notch signaling. More recently, it has been discovered that Notch (especially Notch-1) can exert different, even opposite effects in the same tissue under differing microenvironmental conditions. Further complicating the understanding of Notch receptors is the recently discovered role for non-canonical Notch signaling. Additionally, the most frequent Notch signaling antagonists used in biological systems have been inhibitors of the transmembrane protease complex γ-secretase, which itself processes a plethora of class one transmembrane proteins and thus cannot be considered a Notch-specific upstream regulator. Here we review the available empirical evidence gathered in recent years concerning Notch receptors and ligands in non-small-cell lung carcinoma (NSCLC). Although an overview of the field reveals seemingly contradicting results, we propose that Notch signaling can be exploited as a therapeutic target in NSCLC and represents a promising complement to the current arsenal utilized to combat this malignancy, particularly in targeting NSCLC tissues under specific environmental conditions, such as hypoxia.

show abstract

Section: The Controversial Role Of Notch-1 In Nsclccontrasting

confidence: 54%

Non-small-cell lung carcinoma: role of the Notch signaling pathway

Barse¹,

Bocchetta²

2015

LCTT

View full text Add to dashboard Cite

show abstract

“…Recent evidence demonstrates that tumor growth is regulated by the cross-talk between endothelial cells and tumor cells [ 18 , 19 ]. As an example, lung carcinoma cells when co-cultured with endothelial cells modify their cellular molecular features that encourage tumor cell survival through an undefined mechanism [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

HSPA12B: a novel facilitator of lung tumor growth

Zhang

et al. 2015

Oncotarget

View full text Add to dashboard Cite

Lung tumor progression is regulated by proangiogenic factors. Heat shock protein A12B (HSPA12B) is a recently identified regulator of expression of proangiogenic factors. However, whether HSPA12B plays a role in lung tumor growth is unknown. To address this question, transgenic mice overexpressing HSPA12B (Tg) and wild-type littermates (WT) were implanted with Lewis lung cancer cells to induce lung tumorigenesis. Tg mice showed significantly higher number and bigger size of tumors than WT mice. Tg tumors exhibited increased angiogenesis and proliferation while reduced apoptosis compared with WT tumors. Interestingly, a significantly enhanced upregulation of Cox-2 was detected in Tg tumors than in WT tumors. Also, Tg tumors demonstrated upregulation of VEGF and angiopoietin-1, downregulation of AKAP12, and increased eNOS phosphorylation compared with WT tumors. Celecoxib, a selective Cox-2 inhibitor, suppressed the HSPA12B-induced increase in lung tumor burden. Moreover, celecoxib decreased angiogenesis and proliferation whereas increased apoptosis in Tg tumors. Additionally, celecoxib reduced angiopoietin-1 expression and eNOS phosphorylation but increased AKAP12 levels in Tg tumors. Our results indicate that HSPA12B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified HSPA12B as a novel facilitator of lung tumor growth and a potential therapeutic target for the treatment of lung cancer.

show abstract

“…In lung cancer, the deregulation of the Notch pathway is mainly correlated with activating missense mutations mostly affecting the ligand-binding domain (EGF repeats 11 and 12) or the ankyrin domains which lead to a ligand-independent activation [50]. NOTCH1 activating mutations have been defined as a common event in human NSCLC [51] and have been correlated to poor prognosis and response to therapy in lung patients without p53 mutations [52].…”

Section: Mechanisms Of Notch Deregulation In Cancermentioning

confidence: 99%

Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Sparaneo

Fabrizio

Muscarella

2016

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The transcription factor Nrf2 (NF-E2 related factor 2) is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements) in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

show abstract

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

Cited by 34 publications

References 37 publications

Non-small-cell lung carcinoma: role of the Notch signaling pathway

Non-small-cell lung carcinoma: role of the Notch signaling pathway

HSPA12B: a novel facilitator of lung tumor growth

Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Contact Info

Product

Resources

About