The Role of Notch Signaling and Leptin-Notch Crosstalk in Pancreatic Cancer

Harbuzariu, Adriana; Oprea‐Ilies, Gabriela; Gonzalez-Perez, Ruben R.

doi:10.3390/medicines5030068

Cited by 17 publications

(13 citation statements)

References 108 publications

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“…Thus, several data strongly support the involvement of leptin in common endocrine related cancer in women [ 161 ], especially, breast cancer [ 145 , 162 , 163 ]. Additionally, leptin have been suggested as part of the mechanisms involved in the development of obesity-related carcinogenesis in pancreatic [ 164 ], prostate [ 165 ] and colorectal cancer [ 166 ].…”

Section: Leptin As a Mediator Of Inflammationmentioning

confidence: 99%

Role of Leptin in Inflammation and Vice Versa

Pérez-Pérez

Sánchez-Jiménez

Vilariño-García

et al. 2020

IJMS

183

116

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Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity

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Section: Leptin As a Mediator Of Inflammationmentioning

confidence: 99%

Role of Leptin in Inflammation and Vice Versa

Pérez-Pérez

Sánchez-Jiménez

Vilariño-García

et al. 2020

IJMS

183

116

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“…Researchers have revealed that Notch signaling pathway plays a critical effect on tumor formation and progression 11–14 . Moreover, studies have found that activation of the Notch signaling pathway can promote tumor cell proliferation, which is related to the occurrence of many solid tumors, such as breast cancer and pancreatic cancer 15,16 . In summary, this study aim to reveal whether MEHP exposure can affect the proliferation of NB by regulating the Notch signaling pathway.…”

Section: Introductionmentioning

confidence: 94%

Role of Notch pathway in effect of mono‐2‐ethylhexyl phthalate on the proliferation and cell cycle of SH‐SY5Y cell

Zhang

et al. 2021

Environmental Toxicology

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Neuroblastoma (NB) is an estrogen‐dependent tumor. Mono‐2‐ethylhexyl phthalate (MEHP) has an estrogen‐like effect. However, the effects of MEHP on the progression of NB are not well illustrated. This study was to clarify the effect of Notch pathway on proliferation and cell cycle of SH‐SY5Y cell induced by MEHP. The viability of SH‐SY5Y and BE2C cells were detected by CCK8; cell cycle and apoptosis were detected by flow cytometry; the protein expression levels of Notch pathway and cell cycle related proteins were detected by Western‐blot. Results show that MEHP exposure can promote cell proliferation and altered the cell cycle. MEHP exposure can up‐regulate the expression of C‐MYC, Cyclin D1, Bcl‐2 and affected the Notch pathway. In conclusion, MEHP exposure can promote NB cell proliferation and affect the cell cycle and apoptosis. Notch pathway plays a critical role in accelerating the cell cycle and inhibiting the apoptosis of SH‐SY5Y cells caused by MEHP.

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“…The combination of gemcitabine and Notch-targeting agents has been abundantly studied in pancreatic cancer. Different Notch receptors and ligands contribute to EMT, CSC maintenance, stroma-induced resistance, and to the crosstalk with survival pathways such as NF-κB and PI3K/AKT, favoring the survival of resistant pancreatic clones [570]. Reasonably, combinations of different GSI and Notch-targeting antibodies affected various mechanisms of gemcitabine resistance and improved its anti-viability effects in in vitro experiments.…”

Section: Gemcitabinementioning

confidence: 99%

Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives

Zhdanovskaya

Firrincieli

Lazzari

et al. 2021

Cancers

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Notch signaling guides cell fate decisions by affecting proliferation, apoptosis, stem cell self-renewal, and differentiation depending on cell and tissue context. Given its multifaceted function during tissue development, both overactivation and loss of Notch signaling have been linked to tumorigenesis in ways that are either oncogenic or oncosuppressive, but always context-dependent. Notch signaling is critical for several mechanisms of chemoresistance including cancer stem cell maintenance, epithelial-mesenchymal transition, tumor-stroma interaction, and malignant neovascularization that makes its targeting an appealing strategy against tumor growth and recurrence. During the last decades, numerous Notch-interfering agents have been developed, and the abundant preclinical evidence has been transformed in orphan drug approval for few rare diseases. However, the majority of Notch-dependent malignancies remain untargeted, even if the application of Notch inhibitors alone or in combination with common chemotherapeutic drugs is being evaluated in clinical trials. The modest clinical success of current Notch-targeting strategies is mostly due to their limited efficacy and severe on-target toxicity in Notch-controlled healthy tissues. Here, we review the available preclinical and clinical evidence on combinatorial treatment between different Notch signaling inhibitors and existent chemotherapeutic drugs, providing a comprehensive picture of molecular mechanisms explaining the potential or lacking success of these combinations.

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The Role of Notch Signaling and Leptin-Notch Crosstalk in Pancreatic Cancer

Cited by 17 publications

References 108 publications

Role of Leptin in Inflammation and Vice Versa

Role of Leptin in Inflammation and Vice Versa

Role of Notch pathway in effect of mono‐2‐ethylhexyl phthalate on the proliferation and cell cycle of SH‐SY5Y cell

Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives

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