Cellular Basis Of Action Of Gastrointestinal Peptides/Growth factors

在这一年里，我们撰写了一些特邀综述和批评性分析，其中部分是基于我们对各种胃肠肽(蛙皮素受体家族、VIP-PACAP肽家族、内皮素受体家族、神经降压素)的细胞作用基础的研究。这些文章包括报道了通过EGF受体家族的反式激活而激活一些这些受体对肿瘤生长的影响，以及分别综述了PACAP/VIP和蛙皮素受体家族在各种人类疾病和中枢神经系统癌症中可能的治疗作用。 最近的研究表明，在正常组织和肿瘤组织中，胃肠激素(GI)和GI生长因子(GF)可能通过刺激细胞内多个酪氨酸/丝氨酸/苏氨酸磷酸化(TyrP)信号级联以及通过反式激活生长因子受体而导致细胞生长。然而，目前对许多胃肠激素/生长因子激活这些级联反应的能力知之甚少。在今年的一项研究中，我们报道了肺癌细胞中的神经肽PACAP刺激这些肿瘤的生长，同时主要通过转录激活一些EGFR家族成员，包括EGFR，HER2和HER3来刺激这些肿瘤的生长。在这些细胞中，PACAP刺激EGFR/HER3和HER2/HER3二聚体的形成，从而导致细胞增殖。最近的研究，包括我们的研究表明，在不同的细胞中，这些多肽刺激酪氨酸磷酸化和受体酪氨酸激酶的机制涉及许多不同的机制，在今年的一次应邀综述中，我们对PACAP-VIP、蛙皮素、内皮素和神经降压素进行了详细的综述。这些GPCRs激活这些酪氨酸激酶级联的新能力正在证明这些受体在许多生理/病理过程中的重要性，特别是正常组织和癌症组织的生长级联，开辟了新的治疗方法。

During the year we have written a number of invited reviews and critical analyses which are partially based on our studies of the cellular basis of action of various gastrointestinal peptides (bombesin receptor family, VIP-PACAP peptide family, endothelin receptor family, neurotensin. These include papers reporting the effects of activation of a number of these receptors on cancer growth through the transactivation of the EGF receptor family as well as reviews of the possible therapeutic roles of PACAP/VIP and bombesin receptor families in various human diseases and CNS cancers, respectively. Recent studies show that in both normal and neoplastic tissues, gastrointestinal hormones (GI) and GI growth factors (GF) may cause cell growth by stimulating multiple intracellular tyrosine/serine/threonine phosphorylation (TyrP) signaling cascades as well as by transactivation of growth factor receptors. However, at present little is known about the ability of many gastrointestinal hormones/growth factors to activate these cascades. In a study this year we report that the neuropeptide, PACAP in lung cancer cells stimulates growth of these tumors while signaling principally by transactivation of a number of EGFR family members including EGFR, HER2 and HER3. In these cells PACAP stimulated the formation of EGFR/HER3 and HER2/HER3 dimers resulting in proliferation. Recent studies, including ours have demonstrated that in different cells the mechanisms of the ability of these peptides to stimulate tyrosine phosphorylation and receptor tyrosine kinases involves a number of different mechanisms, and this was reviewed in detail for PACAP-VIP, Bombesin, endothelin and neurotensin in an invited review this year. The novel abilities of these GPCRs to activate these tyrosine kinase cascades are demonstrating the importance of these receptors in numerous physiological/pathological processes, particular growth cascades of both normal and cancer tissues, opening new therapeutic approaches.