Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110134, P.R. China.
Department of Otolaryngology, Head and Neck Surgery, The Second People's Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China.
Mol Med Rep. 2024 Dec;30(6). doi: 10.3892/mmr.2024.13355. Epub 2024 Oct 11.
SPARC/osteonectin, CWCV and Kazal‑like domain proteoglycan (SPOCK) is a family of highly conserved multidomain proteins. In total, three such family members, , and , constitute the majority of extracellular matrix glycoproteins. The gene family has been demonstrated to serve key roles in tumor regulation by affecting MMPs, which accelerates the progression of cancer epithelial‑mesenchymal transition. In addition, they can regulate the cell cycle via overexpression, inhibit tumor cell proliferation by inactivating PI3K/AKT signaling and have been associated with numerous microRNAs that influence the expression of downstream genes. Therefore, the SPOCK gene family are potential cancer‑regulating genes. The present review summarizes the molecular structure, tissue distribution and biological function of the SPOCK family of proteins, in addition to its association with cancer. Furthermore, the present review documents the progress made in investigations into the role of SPOCK, whilst also discussing prospects for the future of SPOCK‑targeted therapy, to provide novel ideas for clinical application and treatment.
富含半胱氨酸的血管生成诱导因子(SPARC)/骨粘连蛋白、卷曲螺旋结构域和 Kazal 型蛋白酶抑制剂(CCN)家族蛋白是一组高度保守的多功能蛋白。该家族共有 3 个成员, 、 和 ,构成了大多数细胞外基质糖蛋白。研究表明, 基因家族通过影响 MMPs 而在肿瘤调控中发挥关键作用,从而加速癌症上皮-间充质转化的进展。此外,它们可以通过过度表达来调节细胞周期,通过抑制 PI3K/AKT 信号通路来抑制肿瘤细胞增殖,并与许多影响下游基因表达的 microRNAs 相关。因此,SPOCK 基因家族是潜在的癌症调控基因。本综述总结了 SPOCK 家族蛋白的分子结构、组织分布和生物学功能,以及其与癌症的关系。此外,本综述还记录了 SPOCK 作用研究的进展,同时讨论了 SPOCK 靶向治疗的未来前景,为临床应用和治疗提供了新的思路。