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LRP1B:癌症翻译领域中迷失的巨人。

LRP1B: A Giant Lost in Cancer Translation.

作者信息

Príncipe Catarina, Dionísio de Sousa Isabel J, Prazeres Hugo, Soares Paula, Lima Raquel T

机构信息

i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.

Cancer Signalling and Metabolism Group, IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal.

出版信息

Pharmaceuticals (Basel). 2021 Aug 24;14(9):836. doi: 10.3390/ph14090836.

Abstract

Low-density lipoprotein receptor-related protein 1B (LRP1B) is a giant member of the LDLR protein family, which includes several structurally homologous cell surface receptors with a wide range of biological functions from cargo transport to cell signaling. LRP1B is among the most altered genes in human cancer overall. Found frequently inactivated by several genetic and epigenetic mechanisms, it has mostly been regarded as a putative tumor suppressor. Still, limitations in LRP1B studies exist, in particular associated with its huge size. Therefore, LRP1B expression and function in cancer remains to be fully unveiled. This review addresses the current understanding of LRP1B and the studies that shed a light on the LRP1B structure and ligands. It goes further in presenting increasing knowledge brought by technical and methodological advances that allow to better manipulate LRP1B expression in cells and to more thoroughly explore its expression and mutation status. New evidence is pushing towards the increased relevance of LRP1B in cancer as a potential target or translational prognosis and response to therapy biomarker.

摘要

低密度脂蛋白受体相关蛋白1B(LRP1B)是低密度脂蛋白受体(LDLR)蛋白家族的一个巨大成员,该家族包括几个结构同源的细胞表面受体,具有从货物运输到细胞信号传导等广泛的生物学功能。LRP1B是人类癌症中总体变化最频繁的基因之一。它经常因多种遗传和表观遗传机制而失活,大多被视为一种假定的肿瘤抑制因子。然而,LRP1B研究仍存在局限性,尤其是与其巨大的规模相关。因此,LRP1B在癌症中的表达和功能仍有待全面揭示。本综述阐述了目前对LRP1B的认识以及揭示LRP1B结构和配体的研究。它进一步介绍了技术和方法进步带来的越来越多的知识,这些进步使得能够更好地调控细胞中LRP1B的表达,并更全面地探索其表达和突变状态。新证据表明,LRP1B作为癌症的潜在靶点或转化预后及治疗反应生物标志物,其相关性日益增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c01/8469001/b2b7d1fc3a28/pharmaceuticals-14-00836-g001.jpg

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