Scholz Nicole
Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Faculty of Medicine, University Leipzig, Leipzig, Germany.
Front Oncol. 2018 Mar 13;8:59. doi: 10.3389/fonc.2018.00059. eCollection 2018.
In mammals, numerous organ systems are equipped with adhesion G protein-coupled receptors (aGPCRs) to shape cellular processes including migration, adhesion, polarity and guidance. All of these cell biological aspects are closely associated with tumor cell biology. Consistently, aberrant expression or malfunction of aGPCRs has been associated with dysplasia and tumorigenesis. Mounting evidence indicates that cancer cells comprise viscoelastic properties that are different from that of their non-tumorigenic counterparts, a feature that is believed to contribute to the increased motility and invasiveness of metastatic cancer cells. This is particularly interesting in light of the recent identification of the mechanosensitive facility of aGPCRs. aGPCRs are signified by large extracellular domains (ECDs) with adhesive properties, which promote the engagement with insoluble ligands. This configuration may enable reliable force transmission to the ECDs and may constitute a molecular switch, vital for mechano-dependent aGPCR signaling. The investigation of aGPCR function in mechanosensation is still in its infancy and has been largely restricted to physiological contexts. It remains to be elucidated if and how aGPCR function affects the mechanoregulation of tumor cells, how this may shape the mechanical signature and ultimately determines the pathological features of a cancer cell. This article aims to view known aGPCR functions from a biomechanical perspective and to delineate how this might impinge on the mechanobiology of cancer cells.
在哺乳动物中，许多器官系统都配备了粘附性G蛋白偶联受体（aGPCRs），以塑造包括迁移、粘附、极性和导向在内的细胞过程。所有这些细胞生物学方面都与肿瘤细胞生物学密切相关。一致的是，aGPCRs的异常表达或功能障碍与发育异常和肿瘤发生有关。越来越多的证据表明，癌细胞具有与非致瘤对应细胞不同的粘弹性特性，这一特征被认为有助于转移性癌细胞的运动性和侵袭性增加。鉴于最近对aGPCRs机械敏感功能的鉴定，这一点尤其有趣。aGPCRs的特征是具有粘附特性的大细胞外结构域（ECDs），其促进与不溶性配体的结合。这种结构可能使力可靠地传递到ECDs，并可能构成一个分子开关，对机械依赖性aGPCR信号传导至关重要。对aGPCRs在机械感觉中的功能研究仍处于起步阶段，并且在很大程度上局限于生理背景。aGPCRs功能是否以及如何影响肿瘤细胞的机械调节，这如何塑造机械特征并最终决定癌细胞的病理特征，仍有待阐明。本文旨在从生物力学角度审视已知的aGPCRs功能，并描述这可能如何影响癌细胞的力学生物学。
