CAFs-derived rho-associated kinase1 mediated EMT to promote laryngeal squamous cell carcinoma metastasis

BackgroundCancer-associated fibroblasts (CAFs) play an essential role in tumorigenesis and development of cancers. Nevertheless, the specific molecular mechanism of tumorigenesis and development in Laryngeal squamous cell carcinoma (LSCC) still unknown.MethodsCAFs, CPFs and NFs were isolated and identified from laryngeal cancer, para-laryngeal cancer and normal tissues. Immunofluorescent staining, Rt-PCR and Western Blot were used to detect the expression of related proteins. Wound healing, migration, invasion and animal experiments were used to examine the ability of movement, migration, invasion and metastasis of LSCC.ResultsROCK1, was highly expressed in CAFs and CAFs enhanced LSCC metastasis in vivo and vitro, and downregulation of ROCK1 in CAFs inhibited the migration and invasion of LSCC cells. While increasing ROCK1 expression in NFs promoted the migration and invasion of LSCC cells. Further studies revealed that epithelial-mesenchymal transition (EMT) and JAK2/STAT3/ERK1/2 pathway might play an essential role in promoting metastasis of LSCC. In addition, inhibition activity of ROCK1 or JAK2/STAT3/ERK1/2 signal molecules significantly reduced EMT and metastasis.ConclusionsCAFs-derived ROCK1 via JAK2/STAT3/ERK1/2 axis mediated EMT to promote LSCC metastasis and targeting ROCK1 might provide a potential treatment strategy for LSCC.

Automated summary

This study found that cancer-associated fibroblasts (CAFs) promote metastasis and development of laryngeal squamous cell carcinoma (LSCC) through the ROCK1-mediated epithelial-mesenchymal transition (EMT) via the JAK2/STAT3/ERK1/2 pathway. Inhibition of ROCK1 or JAK2/STAT3/ERK1/2 signal molecules significantly reduces EMT and metastasis.