Klotho rewires cellular metabolism of breast cancer cells through alteration of calcium shuttling and mitochondrial activity.

Klotho is a transmembrane protein, which can be shed and act as a circulating hormone and is involved in regulating cellular calcium levels and inhibition of the PI3K/AKT pathway. As a longevity hormone, it protects normal cells from oxidative stress, and as a tumor suppressor it inhibits growth of cancer cells. Mechanisms governing these differential activities have not been addressed.

Cell Senescence, DNA Damage, and Metabolism.

Senescence is an essential biological process that blocks tumorigenesis, limits tissue damage, and aids embryonic development. However, once senescent cells accumulate in tissues during aging, they promote the development of age-related diseases and limit health span. Thus, it is essential to expand the boundaries of our knowledge about the mechanisms responsible for controlling cellular senescence.

The Hormone KL1: A Regulator of Breast Cancer Cell Metabolism.

Background: Klotho is a transmembrane protein that can be shed and can act as a circulating hormone in three forms: soluble klotho (KL1 + KL2), KL1, and KL2. Klotho was discovered as a gene implicated in aging through inhibition of the IGF-I pathway. Our laboratory discovered the role of klotho as a tumor suppressor in breast cancer and other malignancies.