?Klotho is a novel marker and cell survival factor in a subset of triple negative breast cancers.

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 ?Klotho, the third member of the Klotho protein family, ?Klotho, is overexpressed in more than 60% of TNBCs and correlates with poorer disease progression. Furthermore, we find that ?Klotho is expressed in a subset of TNBC cell lines promoting cell growth. Importantly, we demonstrate that in these cells ?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 ?Klotho-depleted cells suggesting that ?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 ?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.

SUBMITTER: Trost N 

PROVIDER: S-EPMC4823059 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature