Targeting M3 Muscarinic Receptors for Colon Cancer Therapy.
Targeting M3 Muscarinic Receptors for Colon Cancer Therapy.
复制标题
DOI：
10.2174/1874467211666180119115828
复制
发表时间：
2018
影响因子：
2.7
通讯作者：
Raufman JP
中科院分区：
文献类型：
--
作者：
Felton J;Hu S;Raufman JP
毒蕈碱受体亚型3（M3 R）的表达和激活在结直肠肿瘤的进展中起着重要作用。在本文中，我们描述了毒蕈碱受体在结肠癌中的作用，特别关注M3 R，说明M3 R过表达和受体后信号传导途径的激活如何增强肿瘤进展，并探索可以靶向所涉及分子的各种治疗方法的疗效和安全性。结肠癌过表达M3 R mRNA（CHRM 3）和蛋白质，M3 R后信号刺激细胞增殖。M3 R后信号转导是一个复杂的过程，涉及表皮生长因子受体（EGFR）/ERK和蛋白激酶C（PKC）/p38丝裂原活化蛋白（MAP）激酶信号通路之间的相互作用。特别是，侵袭性和转移性表型的发展需要这些信号相互作用增加关键胶原酶，基质金属蛋白酶-1（MMP-1）的细胞释放。阻断M3 R活化或M3 R后信号传导可减弱MMP 1释放和结肠癌侵袭性。解析这些信号相互作用的复杂性是重要的，不仅要了解这些癌症的发生和发展机制，而且要开发新的治疗方式。由于绝大多数结肠癌患者死于播散性疾病，因此通过靶向M3 R、后M3 R信号传导或MMP 1来预防或逆转癌细胞的转移性扩散具有治疗潜力。
Expression and activation of subtype-3 muscarinic receptors (M3R) plays an important role in the progression of colorectal neoplasia. Herein, we describe the role of muscarinic receptors in colon cancer, focusing specifically on M3R, illustrate how M3R over-expression and activation of post - receptor signaling pathways potentiates tumor progression, and explore the efficacy and safety of a variety of therapeutic approaches that can target the molecules involved. Colon cancers overexpress M3R mRNA (CHRM3) and protein, and post-M3R signaling stimulates cell proliferation. Post-M3R signal transduction is complex, involving interplay between epidermal growth factor receptors (EGFR)/ERK and protein kinase C (PKC)/p38 mitogen-activated protein (MAP) kinase signaling pathways. In particular, the development of an invasive and metastatic phenotype requires that these signaling interactions augment cellular release of a key collagenase, matrix metalloproteinase-1 (MMP1). Blocking either M3R activation or post-M3R signaling attenuates MMP1 release and colon cancer invasiveness. Parsing the complexities of these signaling interactions is important, not only to understand these mechanisms of cancer initiation and progression, but also to develop novel treatment modalities. Since the vast majority of persons with colon cancer die from disseminated disease, preventing or reversing metastatic spread of cancer cells by targeting M3R, post-M3R signaling, or MMP1 has therapeutic potential.
登录
查看更多内容
影响因子：
1.9
作者：
Langenskiold, Marcus;Ivarsson, Marie-Lois;Angenete, Eva
通讯作者：
Angenete, Eva
影响因子：
6.9
作者：
Giambernardi, TA;Grant, GM;Klebe, RJ
通讯作者：
Klebe, RJ
影响因子：
5.8
作者：
Cheng, KR;Raufman, JP
通讯作者：
Raufman, JP
影响因子：
9.6
作者：
Baker, EA;Bergin, FG;Leaper, DJ
通讯作者：
Leaper, DJ
影响因子：
37.3
作者：
Cheng K;Xie G;Khurana S;Heath J;Drachenberg CB;Timmons J;Shah N;Raufman JP
通讯作者：
Raufman JP