γKlotho and cancer

Eye lens-specific γKlotho protects against oxidative stress in cancer

Klotho proteins were discovered as coreceptors for endocrine fibroblast growth factors. Given their role in metabolism, the bonafide members of the Klotho family, αKlotho and βklotho act as tumor suppressors in cancer. Intriguingly, we have found that the third member, γKlotho is a novel marker of a subset of triple-negative breast cancer. We found that γKlotho is normally expressed selectively in the eye lens, but gets overexpressed in tumors and promotes cancer cell growth. We have shown that it does so by protecting cancer cells against oxidative stress. With our studies in human breast cancer cells and canine mammary carcinoma, we aim to identify the underlying molecular mechanism and potential novel therapeutic avenues.

The current projects are:

  • Determine the molecular mechanism of γKlotho-protective function.
  • Determine the role of γKlotho in canine mammary carcinoma.

Relevant publications:

  • Fon Tacer et al., Mol Endo 2010
  • Trošt et al. Oncotarget 2015

The figure depicts three Klotho proteins as three Greek fates – Klothos that hold the thread of life of the cancer cells. Cover art by Jenny Weon, MD, PhD, for Oncotarget Vol 7, No 3.