Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Munster, Germany.
Int J Mol Sci. 2021 Dec 23;23(1):146. doi: 10.3390/ijms23010146.
Cancer progression with uncontrolled tumor growth, local invasion, and metastasis depends largely on the proteolytic activity of numerous matrix metalloproteinases (MMPs), which affect tissue integrity, immune cell recruitment, and tissue turnover by degrading extracellular matrix (ECM) components and by releasing matrikines, cell surface-bound cytokines, growth factors, or their receptors. Among the MMPs, MMP-14 is the driving force behind extracellular matrix and tissue destruction during cancer invasion and metastasis. MMP-14 also influences both intercellular as well as cell-matrix communication by regulating the activity of many plasma membrane-anchored and extracellular proteins. Cancer cells and other cells of the tumor stroma, embedded in a common extracellular matrix, interact with their matrix by means of various adhesive structures, of which particularly invadopodia are capable to remodel the matrix through spatially and temporally finely tuned proteolysis. As a deeper understanding of the underlying functional mechanisms is beneficial for the development of new prognostic and predictive markers and for targeted therapies, this review examined the current knowledge of the interplay of the various MMPs in the cancer context on the protein, subcellular, and cellular level with a focus on MMP14.
癌症的进展伴随着不受控制的肿瘤生长、局部侵袭和转移，在很大程度上取决于许多基质金属蛋白酶（MMPs）的蛋白水解活性，这些酶通过降解细胞外基质（ECM）成分和释放基质细胞因子、细胞表面结合的细胞因子、生长因子或其受体，影响组织完整性、免疫细胞募集和组织更新。在 MMPs 中，MMP-14 是癌症侵袭和转移过程中细胞外基质和组织破坏的驱动力。MMP-14 还通过调节许多质膜锚定和细胞外蛋白的活性，影响细胞间以及细胞-基质通讯。嵌入在共同细胞外基质中的癌细胞和肿瘤基质中的其他细胞通过各种粘附结构与基质相互作用，其中侵袭伪足特别能够通过时空精细调节的蛋白水解来重塑基质。由于深入了解潜在的功能机制有利于开发新的预后和预测标志物以及靶向治疗，因此，本综述在蛋白质、亚细胞和细胞水平上检查了各种 MMPs 在癌症背景下相互作用的最新知识，重点是 MMP14。
