GTSE1 is a Microtubule Plus-end Tracking Protein that Regulates EB1-dependent Cell Migration

21. M.SCOLZ; P.WIDLUND; S.PIAZZA; D.R.BUBLIK; S.REBER; L.Y.PECHE; Y.CIANI; N.HUBNER; M.ISOKANE; M. MONTE; J.ELLENBERG; A.HYMAN; C.SCHNEIDER; A.BIRD

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 vol. 7 p. 51259 - 51269

1932-6203

Cell adhesion and cell migration are two key processes contributing to invasion and metastasis of tumor cells when misregulated.These activities are microtubule-dependent and interrelated: microtubules can control migration through targeted disassembly of focal adhesions.These and other microtubule-dependent processes are facilitated by a large spectrum of microtubule-associated proteins (MAPs), including the microtubule plus-end tracking protein family (+TIPs).Here we identify the protein GTSE1 as a novel MAP and +TIP.GTSE1 interacts directly with microtubules in interphase, where it is also enriched at growing microtubule plus ends through interaction with the EB1 +TIP.The EB1-dependent +TIP activity of GTSE1 is required for microtubule-dependent disassembly of focal adhesions. In non-transformed cells, GTSE1 protein accumulates only in the S and G2 phases of the cell cycle, while in several transformed cell lines its level remains upregulated during G1, where cell migration and invasion processes are most effective.By modulating GTSE1 expression levels in different cell lines, we show that GTSE1 levels determine their migratory capacity.Furthermore, analysis of GTSE1 expression over breast cancer tumors show a significant correlation of GTSE1 expression levels with cancer progression and metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential.