Significance of Trask protein interactions in brain metastatic cohorts of lung cancers

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• 作者：Hua Wu ; Li-qun Shang ; Rui-lin Chen ; Shu-mei Yang ; Shui-li Wang ; Jun Wang…
• 关键词：Integrins ; ADAM ; Metastasis ; Aggressive cancer ; Brain metastasis
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：36
• 期：6
• 页码：4181-4187
• 全文大小：1,057 KB
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• 作者单位：Hua Wu (1)
  Li-qun Shang (1)
  Rui-lin Chen (1)
  Shu-mei Yang (1)
  Shui-li Wang (1)
  Jun Wang (1)
  Gang Sun (1)
  
  1. Department of Respiratory Medicine, Shaanxi Provincial People鈥檚 Hospital, No. 256, Youyi West Road, Beilin District, Xi鈥檃n, 710068, Shaanxi, China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

A class of adhesion protein that occurs in the membrane with both extracellular and intracellular domain and play vital role in maintaining multicellularity is TRASK, also called CUB-domain containing protein1, CD318 (CDCP1). Specifically, in the current study, documented aggressive grades of lung cancers and distant metastatic tissues were examined for protein interactions of Trask and compared with lung cancer variants in situ. The intracellular domain of Trask has the ability to undergo tyrosine phosphorylation and thereafter undergo increased genomic expression, as well as interact with cytoskeletal proteins in the cell periphery and other local signal transduction machinery to induce invadopodia formation and distant metastasis. We incorporated proximity ligation assay to examine protein interactions of Trask in metastatic lung cancer tissues and compare with advanced and low-grade lung cancers restricted to the primary site of origins. Here, we provide direct evidence that activated Trask, which is a phosphorylated form, binds with cytoskeletal proteins actin and spectrin. These interactions were not seen in locally growing lung cancer and cancer in situ. These interactions may be responsible for invadopodia formation and breaking free from a multicellular environment. Functional studies demonstrated interaction between Trask and the STOCs Orai1 and Stim1. Calcium release from internal stores was highest in metastatic lung cancers, suggesting this mechanism as an initial stimulus for the cells to respond chaotically to external growth factor stimulation, especially in aggressive metastatic variants of lung cancers. Recently, inhibitors of STOCs have been identified, and preclinical evidence may be obtained whether these drugs may be of benefit in preventing the deadly consequences of lung cancer.