S100P interacts with integrin α7 and increases cancer cell migration and invasion in lung cancer.
S100P interacts with integrin α7 and increases cancer cell migration and invasion in lung cancer.
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DOI：
10.18632/oncotarget.4987
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发表时间：
2015-10-06
期刊：
影响因子：
--
通讯作者：
Kuo PL
中科院分区：
文献类型：
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作者：
Hsu YL;Hung JY;Liang YY;Lin YS;Tsai MJ;Chou SH;Lu CY;Kuo PL
S100 P是一种钙离子结合蛋白，在多种癌症中过度表达。然而，其在肺癌中的功能特征在很大程度上仍然未知。在这项研究中，我们发现S100 P增加了肺癌细胞的迁移、侵袭和转移。S100 P的异位表达增加了低侵袭性CL 1 -0肺癌细胞的迁移、侵袭和EMT。相反，敲低S100 P抑制迁移和侵袭，并导致高度侵袭性肺癌细胞EMT逆转。这些作用通过增加S100 P与整合素α7的相互作用来转导，整合素α7激活粘着斑激酶（FAK）和AKT。阻断FAK通过降低Src和AKT的激活显著降低S100 P诱导的迁移，而抑制AKT则降低S100 P对ZEB 1表达的上调。进一步的研究表明，S100 P敲低可以防止高转移性人肺癌在动物模型中的扩散。因此，这项研究表明，S100 P代表了肺癌转移的关键激活剂。检测和靶向治疗表达S100 P的癌症是治疗肺癌的一种有吸引力的治疗策略。
S100P, a Ca2+ binding protein, has been shown to be overexpressed in various cancers. However, its functional character in lung cancer remains largely unknown. In this study, we show that S100P increases cancer migration, invasion and metastasis in lung cancer cells. Ectopic expression of S100P increases migration, invasion and EMT in less invasive CL1-0 lung cancer cells. Conversely, knockdown of S100P suppressed migration and invasion, and caused a reversion of EMT in highly invasive lung cancer cells. These effects were transduced by increasing the interaction of S100P with integrin α7, which activated focal adhesion kinase (FAK) and AKT. Blocking FAK significantly decreased S100P-induced migration by decreasing Src and AKT activation, whereas inhibiting AKT reduced S100P upregulation on ZEB1 expression. Further study has indicated that S100P knockdown prevents the spread of highly metastatic human lung cancer in animal models. This study therefore suggests that S100P represents a critical activator of lung cancer metastasis. Detection and targeted treatment of S100P-expressing cancer is an attractive therapeutic strategy in treating lung cancer.