Jang Imjoo, Beningo Karen A
Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
Cancers (Basel). 2019 May 24;11(5):721. doi: 10.3390/cancers11050721.
Cells respond to both chemical and mechanical cues present within their microenvironment. Various mechanical signals are detected by and transmitted to the cells through mechanoreceptors. These receptors often contact with the extracellular matrix (ECM), where the external signals are converted into a physiological response. Integrins are well-defined mechanoreceptors that physically connect the actomyosin cytoskeleton to the surrounding matrix and transduce signals. Families of α and β subunits can form a variety of heterodimers that have been implicated in cancer progression and differ among types of cancer. These heterodimers serve as the nexus of communication between the cells and the tumor microenvironment (TME). The TME is dynamic and composed of stromal cells, ECM and associated soluble factors. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs). Accumulating studies implicate CAFs in cancer development and metastasis through their remodeling of the ECM and release of large amounts of ECM proteins and soluble factors. Considering that the communication between cancer cells and CAFs, in large part, takes place through the ECM, the involvement of integrins in the crosstalk is significant. This review discusses the role of integrins, as the primary cell-ECM mechanoreceptors, in cancer progression, highlighting integrin-mediated mechanical communication between cancer cells and CAFs.
细胞对其微环境中存在的化学和机械信号均会产生响应。各种机械信号通过机械感受器被细胞检测到并传递给细胞。这些感受器通常与细胞外基质（ECM）接触，在那里外部信号被转化为生理反应。整合素是明确的机械感受器，它将肌动球蛋白细胞骨架与周围基质物理连接并传导信号。α和β亚基家族可以形成多种异二聚体，这些异二聚体与癌症进展有关，且在不同类型的癌症中有所不同。这些异二聚体是细胞与肿瘤微环境（TME）之间通讯的枢纽。TME是动态的，由基质细胞、ECM和相关的可溶性因子组成。TME中最丰富的基质细胞是癌症相关成纤维细胞（CAF）。越来越多的研究表明，CAF通过重塑ECM以及释放大量ECM蛋白和可溶性因子参与癌症的发展和转移。鉴于癌细胞与CAF之间的通讯在很大程度上是通过ECM进行的，整合素在这种相互作用中的参与具有重要意义。本综述讨论了作为主要细胞-ECM机械感受器的整合素在癌症进展中的作用，重点强调了整合素介导的癌细胞与CAF之间的机械通讯。
