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TM4SF1 通过与整合素 α6 相互作用促进食管鳞癌细胞转移。

TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6.

机构信息

Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, 225009, Yangzhou, Jiangsu, China.

Department of Clinical Medicine, Medical College, Yangzhou University, 225001, Yangzhou, Jiangsu, China.

出版信息

Cell Death Dis. 2022 Jul 14;13(7):609. doi: 10.1038/s41419-022-05067-2.

DOI:10.1038/s41419-022-05067-2
PMID:35835740
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9283456/
Abstract

Transmembrane-4 L-six family member-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate tumor cell behaviors. However, the function and mechanism of TM4SF1 in esophageal squamous cell carcinoma (ESCC) metastasis remains unclear. Here, we find that TM4SF1 expression is increased and positively correlated with clinical TNM stage, N classification, differentiation, tumor size, and poor prognosis in ESCC patients. Interestingly, we demonstrate that TM4SF1 promotes ESCC cell adhesion, spreading, migration, and invasion, but not cell proliferation, in a laminin-dependent manner by interacting with integrin α6. Mechanistically, the TM4SF1/integrin α6/FAK axis signal pathway mediates cell migration under laminin-coating condition. Inhibiting FAK or knocking down TM4SF1 can attenuate TM4SF1-mediated cell migration and lung metastasis. Clinically, the TM4SF1/integrin α6/FAK axis positively correlates with ESCC. Altogether, these findings reveal a new mechanism of TM4SF1 in promoting ESCC metastasis via binding to integrin α6 and suggest that the cross-talk between TM4SF1 and integrin α6 may serve as a therapeutic target for ESCC.

摘要

跨膜 4 L-六家族成员 1（TM4SF1）是 L6 家族的成员，作为信号转导物调节肿瘤细胞行为。然而，TM4SF1 在食管鳞状细胞癌（ESCC）转移中的功能和机制尚不清楚。在这里，我们发现 TM4SF1 表达增加，并与 ESCC 患者的临床 TNM 分期、N 分类、分化、肿瘤大小和不良预后呈正相关。有趣的是，我们证明 TM4SF1 通过与整合素 α6 相互作用，以层粘连蛋白依赖的方式促进 ESCC 细胞黏附、铺展、迁移和侵袭，但不促进细胞增殖。在机制上，TM4SF1/整合素 α6/FAK 轴信号通路介导了层粘连蛋白包被条件下的细胞迁移。抑制 FAK 或敲低 TM4SF1 可减弱 TM4SF1 介导的细胞迁移和肺转移。临床上，TM4SF1/整合素 α6/FAK 轴与 ESCC 呈正相关。总之，这些发现揭示了 TM4SF1 通过与整合素 α6 结合促进 ESCC 转移的新机制，并表明 TM4SF1 和整合素 α6 之间的串扰可能成为 ESCC 的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/8210ee147e7f/41419_2022_5067_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/1f1af76e9d6d/41419_2022_5067_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/9018e6f46e91/41419_2022_5067_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/67ca0c0ff187/41419_2022_5067_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/9c7d9aa68d18/41419_2022_5067_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/e6407e8a529c/41419_2022_5067_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/a9ff8a67f7b5/41419_2022_5067_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/8210ee147e7f/41419_2022_5067_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/1f1af76e9d6d/41419_2022_5067_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/9018e6f46e91/41419_2022_5067_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/67ca0c0ff187/41419_2022_5067_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/9c7d9aa68d18/41419_2022_5067_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/e6407e8a529c/41419_2022_5067_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/a9ff8a67f7b5/41419_2022_5067_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1a9/9283456/8210ee147e7f/41419_2022_5067_Fig7_HTML.jpg

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