Notch signaling where pancreatic cancer and differentiation meet

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

notch signaling where pancreatic cancer and differentiation meet

Purpose: Aberrant activation of the Notch signaling pathway is commonly observed in human pancreatic cancer, although the mechanism(s) for this activation. See “Inhibition of γ-secretase activity inhibits tumor progression in a mouse model of pancreatic ductal adenocarcinoma” by Plenty R, Park JS. Loading. AACR Annual Meeting-- Apr , ; Denver, CO However, the exact role of Notch signaling in pancreatic cancer development is not fully understood. that Notch-positive cells could trans-differentiate to Notch-negative cells.

Abstract There is accumulating evidence that deregulated Notch signaling affects cancer development, and specifically pancreatic cancer PC progression. Notch canonical and non-canonical signaling has diverse impact on PC. Moreover, the actions of RBP-Jk nuclear partner of activated Notch independent of Notch signaling pathway seem to affect differently cancer progression. The potential pivotal role of leptin on PC, and its connection with Notch signaling and chemoresistance are still not completely understood.

  • Targeting Notch signalling pathway of cancer stem cells
  • Notch signaling: where pancreatic cancer and differentiation meet?

We will also discuss on the novel crosstalk between leptin and Notch in PC and its implications in chemoresistance. Data from these investigations could help to open unexplored ways to improve PC treatment success that has shown little progress for many years.

Notch signaling: where pancreatic cancer and differentiation meet?

Introduction PC is one of the most malignant and chemotherapy-resistant tumors. That is mainly due to the lack of effective diagnosis at an early stage of tumor development and ineffective therapy. Resectable tumors at detection time comprise a low percentage of PC.

Majority of PC are treated with non-specific target therapies, i. Multiple mechanisms are involved in PC chemoresistance, including aberrant gene expression, deregulation of key signaling pathways, development of the epithelial-mesenchymal transition EMTcancer stem cells and desmoplasia [ 1 ].

notch signaling where pancreatic cancer and differentiation meet

A factor involved in cancer chemoresistance is the activation and deregulation of the Notch signaling pathway. Notch signaling has been recently linked to 5-FU resistance in PC [ 2 ]. None; IV Collection and assembly of data: None; VI Manuscript writing: All authors; V Final approval of manuscript: Received Nov 24; Accepted Jan Copyright Stem Cell Investigation.

This article has been cited by other articles in PMC. Abstract Cancer stem cells CSCs have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor.

CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer.

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

The CSCs like any other stem cells activate the signal transduction pathways that involve the development and tissue homeostasis, which include Notch signaling pathway.

The new treatment targets these pathway that control stem-cell replication, survival and differentiation that are under development. Notch inhibitors either single or in combination with chemotherapy drugs have been developed to treat cancer and its recurrence.

notch signaling where pancreatic cancer and differentiation meet

This approach of targeting signaling pathway of CSCs represents a promising future direction for the therapeutic strategy to cure cancer. These stem cells play a vital role in growth and development of the cancerous tumors. Many studies have shown that the CSCs are the progenitor of the tumor and are the reason for recurrence of cancer.