GTSE1 Is a Microtubule Plus-End Tracking Protein That Regulates EB1-Dependent Cell Migration

Abstract

The regulation of cell migration is a highly complex process that is often compromised when cancer cells become metastatic. The microtubule cytoskeleton is necessary for cell migration, but how microtubules and microtubule-associated proteins regulate multiple pathways promoting cell migration remains unclear. Microtubule plus-end binding proteins (+TIPs) are emerging as important players in many cellular functions, including cell migration. Here we identify a +TIP, GTSE1, that promotes cell migration. GTSE1 accumulates at growing microtubule plus ends through interaction with the EB1+TIP. The EB1-dependent +TIP activity of GTSE1 is required for cell migration, as well as for microtubule-dependent disassembly of focal adhesions. GTSE1 protein levels determine the migratory capacity of both nontransformed and breast cancer cell lines. In breast cancers, increased GTSE1 expression correlates with invasive potential, tumor stage, and time to distant metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential.

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

“…Migration and invasion are important features controlling the metastasis of cancer cells, and these processes require changes to the microtubule cytoskeleton. In breast cancer, alteration of GTSE1 expression is associated with increased invasive potential, and GTSE1 was identified as a microtubule‐associated plus‐end tracking protein, which promotes cell migration through interactions with EB1 . Consistently, we have shown that migration and invasion of AM cells were stimulated by GTSE1 overexpression and suppressed by its depletion.…”

“…Negative regulation of p53 allows cells to resist apoptosis and transition through the G2/M checkpoint, leading to tumor progression. In interphase, GTSE1 accumulates at growing microtubule plus‐ends by interacting with microtubule‐associated protein RP/EB family member 1 (EB1), and its activity is required for cell migration and focal adhesion formation . GTSE1 has been found to play roles in human cancer proliferation, apoptosis, and migration.…”

Anti-Migratory Effect of Vinflunine in Endothelial and Glioblastoma Cells Is Associated with Changes in EB1 C-Terminal Detyrosinated/Tyrosinated Status

“…On the other hand, EB1 appeared to be a more reliable marker as we found a strong correlation between EB1 accumulation at MT (+) ends and the inhibition of endothelial migration by VFL at all effective concentrations. These results are strengthened by recent works demonstrating that EB1 down-regulation impairs migration [35] and capillary-like tube formation in endothelial cells [36]. Taken together these observations make EB1 comets a crucial marker of cell migration and a potential target in neoangiogenesis.…”

The Clathrin-dependent Spindle Proteome

“…GTSE1 is a microtubule plus-end tracking protein (ϩTIP) that binds directly to the microtubules. Its depletion results in disorganized microtubules (52). SENP3 is a SUMO isopeptidase that during mitosis interacts with Borealin, a chromosomal passenger complex protein involved in regulating chromosome congression, the SAC, and cytokinesis (53).…”