Yamashita K, Iwatake M, Okamoto K, Yamada S-I, Umeda M, Tsukuba T
Department of Dental Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Oral Dis. 2017 May;23(4):518-525. doi: 10.1111/odi.12643. Epub 2017 Mar 9.
Cathepsin K was initially discovered as an osteoclast-specific cysteine proteinase, but the enzyme is also expressed in various cancers including oral squamous cell carcinomas. This study aimed to clarify the function of cathepsin K in oral squamous cell carcinomas.
Expression levels of cathepsin K were examined in six types of cell carcinomas. Carcinomas overexpressing cathepsin K were constructed. Effects of cathepsin K overexpression and treatment with odanacatib, a specific cathepsin K inhibitor, on cell invasion, migration and adhesion were analysed.
Different levels of cathepsin K were expressed in carcinomas. Cathepsin K was predominantly localised in lysosomes. Cathepsin K overexpression impaired the proliferation of carcinomas. Invasion analysis showed that cathepsin K overexpression enhanced invasion and migration of carcinomas, whereas inhibition of cathepsin K by odanacatib caused the opposite effects in carcinomas. Cathepsin K overexpression also increased cell adhesion and slightly increased surface expression of the adhesion receptor CD29/integrin β .
The enhanced invasion of carcinomas resulting from cathepsin K overexpression is probably due to the increased cell migration and adhesion. Thus, cathepsin K is implicated not only in protein degradation but also in invasion, migration and adhesion of oral squamous cell carcinomas.
组织蛋白酶K最初被发现是一种破骨细胞特异性半胱氨酸蛋白酶，但该酶也在包括口腔鳞状细胞癌在内的多种癌症中表达。本研究旨在阐明组织蛋白酶K在口腔鳞状细胞癌中的功能。
检测了六种类型细胞癌中组织蛋白酶K的表达水平。构建了过表达组织蛋白酶K的癌组织。分析了组织蛋白酶K过表达以及用特异性组织蛋白酶K抑制剂奥达卡替治疗对细胞侵袭、迁移和黏附的影响。
癌组织中组织蛋白酶K表达水平各异。组织蛋白酶K主要定位于溶酶体。组织蛋白酶K过表达损害了癌组织的增殖。侵袭分析表明，组织蛋白酶K过表达增强了癌组织的侵袭和迁移能力，而奥达卡替抑制组织蛋白酶K则在癌组织中产生相反的作用。组织蛋白酶K过表达还增加了细胞黏附，并使黏附受体CD29/整合素β的表面表达略有增加。
组织蛋白酶K过表达导致癌组织侵袭增强可能是由于细胞迁移和黏附增加。因此，组织蛋白酶K不仅与蛋白质降解有关，还与口腔鳞状细胞癌的侵袭、迁移和黏附有关。
