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松弛素/ RXFP1 系统在癌症治疗中的新作用。

Emerging roles for the relaxin/RXFP1 system in cancer therapy.

机构信息

Department of Human Anatomy and Cell Science, College of Medicine, University of Manitoba, Winnipeg, Canada.

Department of Biology, Acadia University, Wolfville, Nova Scotia, Canada.

出版信息

Mol Cell Endocrinol. 2019 May 1;487:85-93. doi: 10.1016/j.mce.2019.02.001. Epub 2019 Feb 11.

Abstract

A role for the hormone relaxin in cancer was described well before the receptor was identified. Relaxin predominantly increases the growth and invasive potential in cancers of different origins. However, relaxin was also shown to promote cell differentiation and to act in a dose-and time-dependent manner in different cancer cell models used. Following the discovery of the relaxin like family peptide receptor 1 (RXFP1) as the cellular receptor for RLN1 and RLN2, research has focussed on the ligand interaction with the large extracellular domain of RXFP1 and resulting molecular signaling mechanisms. RXFP1 activation mediates anti-apoptotic functions, angiogenesis and chemoresistance in cancer cells. This minireview summarizes the known biological functions of RXFP1 activation in different cancer entities in-vitro and in-vivo and outlines possible mechanisms to therapeutically address the relaxin-RXFP1 system in cancer cells.

摘要

松弛素在癌症中的作用早在受体被鉴定之前就已经被很好地描述了。松弛素主要增加不同来源的癌症的生长和侵袭潜力。然而,松弛素也被证明可以促进细胞分化,并在不同的癌细胞模型中以剂量和时间依赖的方式发挥作用。在发现松弛素样家族肽受体 1(RXFP1)作为 RLN1 和 RLN2 的细胞受体后,研究集中在配体与 RXFP1 的大细胞外结构域的相互作用以及由此产生的分子信号转导机制上。RXFP1 的激活介导了癌细胞的抗凋亡功能、血管生成和化疗耐药性。这篇综述总结了 RXFP1 在不同癌症实体中的已知生物学功能,以及在体外和体内可能的机制,以治疗性地解决癌症细胞中的松弛素-RXFP1 系统。

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