Harbuzariu Adriana, Oprea-Ilies Gabriela M, Gonzalez-Perez Ruben R
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
Medicines (Basel). 2018 Jul 2;5(3):68. doi: 10.3390/medicines5030068.
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. Recent data show that in PC and other cancer types the adipokine leptin can modulate Notch/RBP-Jk signaling, thereby, linking the pandemic obesity with cancer and chemoresistance. The potential pivotal role of leptin on PC, and its connection with Notch signaling and chemoresistance are still not completely understood. In this review, we will describe the most important aspects of Notch-RBP-Jk signaling in PC. Further, we will discuss on studies related to RBP-Jk-independent Notch and Notch-independent RPB-Jk signaling. We will also discuss on the novel crosstalk between leptin and Notch in PC and its implications in chemoresistance. The effects of leptin-Notch/RBP-Jk signaling on cancer cell proliferation, apoptosis, and drug resistance require more investigation. Data from these investigations could help to open unexplored ways to improve PC treatment success that has shown little progress for many years.
越来越多的证据表明，失调的Notch信号传导会影响癌症发展，尤其是胰腺癌（PC）的进展。Notch经典信号传导和非经典信号传导对PC有不同影响。此外，RBP-Jk（活化Notch的核伴侣）独立于Notch信号通路的作用似乎对癌症进展有不同影响。最近的数据表明，在PC和其他癌症类型中，脂肪因子瘦素可以调节Notch/RBP-Jk信号传导，从而将大流行的肥胖与癌症和化疗耐药性联系起来。瘦素在PC中的潜在关键作用及其与Notch信号传导和化疗耐药性的联系仍未完全了解。在本综述中，我们将描述PC中Notch-RBP-Jk信号传导的最重要方面。此外，我们将讨论与RBP-Jk非依赖性Notch和Notch非依赖性RPB-Jk信号传导相关的研究。我们还将讨论PC中瘦素与Notch之间新型的相互作用及其在化疗耐药性中的意义。瘦素-Notch/RBP-Jk信号传导对癌细胞增殖、凋亡和耐药性的影响需要更多研究。这些研究的数据可能有助于开辟未探索的途径，以提高多年来进展甚微的PC治疗成功率。
