Department of Oncology, Ningbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China.
Department of Cardiovascular Division, Ningbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, China.
Aging (Albany NY). 2023 Mar 20;15(6):2097-2114. doi: 10.18632/aging.204594.
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. Identifying key molecular targets related to the initiation, development, and metastasis of lung cancer is important for its diagnosis and target therapy. The ADAMTS families of multidomain extracellular protease enzymes have been reported to be involved in many physiological processes. In this study, we found that ADAMTS1 was highly expressed in NSCLC tissues, which promoted cell proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) of NSCLC cells. In the NSCLC tumor metastasis model involving nude mice, overexpression of ADAMTS1 promoted EMT and lung metastasis of tumor cells. Moreover, ADAMTS1 positively regulated TGF-β expression, and TGF-β was highly expressed in NSCLC tumor tissues. si-TGF-β or inhibition of TGF-β expression through the short peptide KTFR on ADAMTS1 protein could reverse the oncogenic effects of ADAMTS1 on lung cancer cells. Taken together, ADAMTS1 functioned as an oncogene in NSCLC cells by promoting TGF-β expression, indicating that ADAMTS1 has important regulatory roles in the progression of NSCLC.
非小细胞肺癌（NSCLC）约占所有肺癌的 80%。鉴定与肺癌的发生、发展和转移相关的关键分子靶标对于其诊断和靶向治疗非常重要。ADAMTS 家族的多种结构域细胞外蛋白酶已被报道参与许多生理过程。在本研究中，我们发现 ADAMTS1 在 NSCLC 组织中高表达，促进 NSCLC 细胞的增殖、迁移、侵袭和上皮间质转化（EMT）。在涉及裸鼠的 NSCLC 肿瘤转移模型中，ADAMTS1 的过表达促进了肿瘤细胞的 EMT 和肺转移。此外，ADAMTS1 正向调节 TGF-β 的表达，而 TGF-β 在 NSCLC 肿瘤组织中高表达。si-TGF-β 或通过 ADAMTS1 蛋白上的短肽 KTFR 抑制 TGF-β 的表达可以逆转 ADAMTS1 对肺癌细胞的致癌作用。总之，ADAMTS1 通过促进 TGF-β 的表达在 NSCLC 细胞中发挥癌基因作用，表明 ADAMTS1 在 NSCLC 的进展中具有重要的调节作用。
