Yang Liyun, Qiao Peipei, Zhang Jianwei, Chen Xiaoping, Hu An, Huang Shuixian
Department of Otolaryngology, Gongli Hospital, The Second Military Medical University, Shanghai, 200135, China.
Discov Oncol. 2022 Nov 5;13(1):120. doi: 10.1007/s12672-022-00578-y.
We previously found that the Rho-associated kinase 1 (ROCK1) activated Cancer-associated fibroblasts (CAFs) to promote LSCC metastasis. Accumulating evidence indicates that pyridine nucleotide-disulfide oxidoreductase domain 1 (PYROXD1) is an oncogene; however, the crosstalk between ROCK1 and PYROXD1 in LSCC metastasis remains largely unknown. Here, we found that ROCK1 could target PYROXD1. The knockdown of ROCK1 expression reduces the expression of PYROXD1, while the knockdown of PYROXD1 expression did not alter the expression of ROCK1 indicating that ROCK1 is upstream of PYROXD1. Further, LSCC cells cocultured with PYROXD1 knocked-down CAFs exhibited lower proliferation, migration, invasion and metastasis abilities. Conversely, LSCC cells cocultured with PYROXD1-overexpressing CAFs showed opposite results. In conclusion, the crosstalk between ROCK1 and PYROXD1 regulated CAFs activation and promoted LSCC metastasis.
我们之前发现,Rho相关激酶1(ROCK1)激活癌症相关成纤维细胞(CAFs)以促进喉鳞状细胞癌(LSCC)转移。越来越多的证据表明,吡啶核苷酸二硫化物氧化还原酶结构域1(PYROXD1)是一种癌基因;然而,ROCK1与PYROXD1在LSCC转移中的相互作用在很大程度上仍不清楚。在此,我们发现ROCK1可以靶向PYROXD1。敲低ROCK1表达会降低PYROXD1的表达,而敲低PYROXD1表达并不会改变ROCK1的表达,这表明ROCK1在PYROXD1的上游。此外,与敲低PYROXD1的CAFs共培养的LSCC细胞表现出较低的增殖、迁移、侵袭和转移能力。相反,与过表达PYROXD1的CAFs共培养的LSCC细胞则呈现相反的结果。总之,ROCK1与PYROXD1之间的相互作用调节了CAFs的激活并促进了LSCC转移。