Author/Editor		Trošt, Nuša; Peña-Llopis, Samuel; Koirala, Sajjan; Stojan, Jure; Potts, Patrick Ryan; Fon Tacer, Klementina; Martinez, Elisabeth
Title		[Gamma]Klotho is a novel marker and cell survival factor in a subset of triple negative breast cancers
Type		članek
Publication year		2015
ISSN		1949-2553 - Oncotarget
Language		eng
Abstract		Over the last decade, breast cancer mortality has declined. However, triple negative breast cancer (TNBC) remains a challenging problem mostly due to early recurrence and lack of molecularly driven treatments. There is a critical need to identify subgroups of TNBC with common molecular features that can be therapeutically targeted. Here we show that in contrast to Klotho and [gamma]Klotho, the third member of the Klotho protein family, [gamma]Klotho, is overexpressed in more than 60% of TNBCs and correlates with poorer disease progression. Furthermore, we find that [gamma]Klotho is expressed in a subset of TNBC cell lines promoting cell growth. Importantly, we demonstrate that in these cells [gamma]Klotho is necessary for cell survival and that its depletion leads to constitutive ERK activation, cell cycle arrest and apoptosis. Interestingly, we observe increased oxidative stress in [gamma]Klotho-depleted cells suggesting that [gamma]Klotho enables cancer cells to cope with an oxidative environment and that cells become dependent on its expression to maintain this survival advantage. These findings indicate that [gamma]Klotho might be a potential marker for patients that would benefit from treatments that alter oxidative stress and constitutes a novel drug target for a subset of TN breast cancers.
Keywords		rak dojk faktor preživetja celic podskupina breast cancers cell survival factor subset