ADAM10 promotes pituitary adenoma cell migration by regulating cleavage of CD44 and L1

Journal of Molecular Endocrinology
Yuan PanXuehua Ding

Abstract

ADAM10 is a metalloproteinase that regulates invasiveness in many tumors. Here, we found that ADAM10 expression correlates with the invasiveness of pituitary adenomas and contributes to invasion by cleaving L1 and CD44. In high-grade pituitary adenoma patients, ADAM10 expression levels were found to be elevated compared with low-grade pituitary adenomas. In a phorbol 12-myristate 13-acetate (PMA)-stimulated pituitary adenoma cell line, AtT-20 cells, we found that the cleavage of L1 was correspondingly enhanced with the increased interaction between Src and Shc. Increases in PMA-induced L1 cleavage and the phosphorylation of residue 418 of Src (418Src) were promoted by overexpression of ADAM10. Inversely, knockdown of Adam10 suppressed PMA-induced L1 cleavage and the phosphorylation of Src, which was blocked by the Src inhibitor PP2 and the MEK inhibitor PD98059. On the other hand, calcium flux activation in AtT-20 cells resulted in increased CD44 cleavage, with reduction of the interaction between calmodulin and ADAM10. The induction of enhanced CD44 cleavage by calcium flux activation was inhibited by knockdown of Adam10. In addition, Adam10 knockdown repressed AtT-20 cell migration, which was reversed by CD44EXT (CD44 ectodom...Continue Reading

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Citations

Nov 5, 2015·The Journal of Biological Chemistry·James D LondinoRama K Mallampalli
Apr 9, 2019·Chemical Communications : Chem Comm·Tanmay Mondal, Bhubaneswar Mandal
Apr 4, 2017·Frontiers in Molecular Neuroscience·Kristina Endres, Thomas Deller
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Jun 9, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Amir Sadra Zangouei, Meysam Moghbeli

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