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

Liyun Yang; Shiqi Gong; Peipei Qiao; Runyu Zhao; Shuixian Huang; Jieyu Zhou; An Hu

doi:10.1186/s12935-023-02911-z

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

Cancer Cell Int. 2023 Apr 16;23(1):70. doi: 10.1186/s12935-023-02911-z.

Authors

Liyun Yang^#¹, Shiqi Gong^#², Peipei Qiao^#¹, Runyu Zhao^#³, Shuixian Huang⁴, Jieyu Zhou⁵, An Hu⁶

Affiliations

¹ Department of Otolaryngology, Gongli Hospital, the Second Military Medical University, Shanghai, 200135, China.
² Department of Otolaryngology & Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
³ Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135, China.
⁴ Department of Otolaryngology, Gongli Hospital, the Second Military Medical University, Shanghai, 200135, China. hsxent@163.com.
⁵ Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 200011, China. entzhoujieyu@126.com.
⁶ Department of Otolaryngology, Gongli Hospital, the Second Military Medical University, Shanghai, 200135, China. juanitohuan@163.com.

^# Contributed equally.

Abstract

Background: Cancer-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.

Methods: CAFs, 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.

Results: ROCK1, 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.

Conclusions: CAFs-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.

Keywords: CAFs; EMT; JAK2/STAT3/ERK1/2 signal pathway; Metastasis; ROCK1.