Crosstalk of TGF-β and somatostatin signaling in adenocarcinoma and neuroendocrine tumors of the pancreas: a brief review.

IF 3.9 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Frontiers in Endocrinology Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1511348
Hendrik Ungefroren, Harpal Randeva, Hendrik Lehnert, Jörg Schrader, Jens-Uwe Marquardt, Björn Konukiewitz, Ralf Hass
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引用次数: 0

Abstract

Although the vast majority of cancers affecting the human pancreas are pancreatic ductal adenocarcinomas (PDAC), there are several other cancer types originating from non-exocrine cells of this organ, i.e., pancreatic neuroendocrine tumors (panNET). Genomic analyses of PDAC and panNET revealed that certain signaling pathways such as those triggered by transforming growth factor-β (TGF-β) are frequently altered, highlighting their crucial role in pancreatic tumor development. In PDAC, TGF-β plays a dual role acting as a tumor suppressor in healthy tissue and early stages of tumor development but as a promoter of tumor progression in later stages. This peptide growth factor acts as a potent inducer of epithelial-to-mesenchymal transition (EMT), a developmental program that transforms otherwise stationary epithelial cells to invasive mesenchymal cells with enhanced metastatic potential. TGF-β signals through both the canonical Smad pathway involving the receptor-regulated Smad proteins, SMAD2 and SMAD3, and the common-mediator Smad, SMAD4, as well as Smad-independent pathways, i.e., ERK1/2, PI3K/AKT, and somatostatin (SST). Accumulating evidence indicates an intimate crosstalk between TGF-β and SST signaling, not only in PDAC but, more recently, also in panNET. In this work, we review the available evidence on signaling interactions between both pathways, which we believe are of potential but as yet insufficiently appreciated importance for pancreatic cancer development and/or progression as well as novel therapeutic approaches.

TGF-β和生长抑素信号在胰腺腺癌和神经内分泌肿瘤中的串扰研究综述
虽然绝大多数影响人类胰腺的癌症是胰腺导管腺癌(PDAC),但也有几种其他类型的癌症起源于该器官的非外分泌细胞,即胰腺神经内分泌肿瘤(panNET)。PDAC和panNET的基因组分析显示,某些信号通路如转化生长因子-β (TGF-β)触发的信号通路经常发生改变,突出了它们在胰腺肿瘤发展中的关键作用。在PDAC中,TGF-β在健康组织和肿瘤发展早期作为肿瘤抑制因子,在晚期作为肿瘤进展的促进因子发挥双重作用。这种肽生长因子是上皮-间质转化(EMT)的有效诱导剂,EMT是一种将静止上皮细胞转化为侵袭性间质细胞的发育过程,具有增强的转移潜力。TGF-β信号通过典型的Smad通路,包括受体调节的Smad蛋白SMAD2和SMAD3,以及共同介质Smad、SMAD4以及Smad独立通路,即ERK1/2、PI3K/AKT和生长抑素(SST)。越来越多的证据表明,TGF-β和SST信号之间存在密切的串扰,不仅在PDAC中,最近也在panNET中。在这项工作中,我们回顾了两种途径之间信号相互作用的现有证据,我们认为这对胰腺癌的发展和/或进展以及新的治疗方法具有潜在的但尚未充分认识的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Frontiers in Endocrinology
Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.70
自引率
9.60%
发文量
3023
审稿时长
14 weeks
期刊介绍: Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.
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