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癌相关成纤维细胞衍生的Rho相关激酶1介导上皮-间质转化以促进喉鳞状细胞癌转移。

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

作者信息

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

机构信息

Department of Otolaryngology, Gongli Hospital, the Second Military Medical University, Shanghai, 200135, China.

Department of Otolaryngology & Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

出版信息

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

DOI:10.1186/s12935-023-02911-z
PMID:37062850
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10105957/
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.

摘要

背景

癌症相关成纤维细胞（CAFs）在肿瘤发生和发展中起重要作用。然而，喉鳞状细胞癌（LSCC）发生和发展的具体分子机制仍不清楚。

方法

从喉癌、癌旁组织和正常组织中分离并鉴定CAFs、对照成纤维细胞（CPFs）和正常成纤维细胞（NFs）。采用免疫荧光染色、逆转录-聚合酶链反应（Rt-PCR）和蛋白质免疫印迹法检测相关蛋白的表达。采用伤口愈合实验、迁移实验、侵袭实验和动物实验检测LSCC的运动、迁移、侵袭和转移能力。

结果

ROCK1在CAFs中高表达，CAFs在体内外均增强了LSCC的转移，CAFs中ROCK1的下调抑制了LSCC细胞的迁移和侵袭。而在NFs中增加ROCK1的表达则促进了LSCC细胞的迁移和侵袭。进一步研究表明，上皮-间质转化（EMT）和JAK2/STAT3/ERK1/2信号通路可能在促进LSCC转移中起重要作用。此外，抑制ROCK1或JAK2/STAT3/ERK1/2信号分子的活性可显著降低EMT和转移。

结论

CAFs来源的ROCK1通过JAK2/STAT3/ERK1/2轴介导EMT促进LSCC转移，靶向ROCK1可能为LSCC提供一种潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/07ef6885e131/12935_2023_2911_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/a42a2838c5e4/12935_2023_2911_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/fa739e6b3b78/12935_2023_2911_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/297bc4feadb6/12935_2023_2911_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/321d1fac4255/12935_2023_2911_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/c8219e85c4ba/12935_2023_2911_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/9d9c978ce54c/12935_2023_2911_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/e12c961a1589/12935_2023_2911_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/07ef6885e131/12935_2023_2911_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/a42a2838c5e4/12935_2023_2911_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/fa739e6b3b78/12935_2023_2911_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/297bc4feadb6/12935_2023_2911_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/321d1fac4255/12935_2023_2911_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/c8219e85c4ba/12935_2023_2911_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/9d9c978ce54c/12935_2023_2911_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/e12c961a1589/12935_2023_2911_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb3/10105957/07ef6885e131/12935_2023_2911_Fig8_HTML.jpg

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