The Anti-Aging and Tumor Suppressor Protein Klotho Affects Signaling Pathwaysin a Human Oligodendroglioma Cell Line

Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here we examined the effects of Klotho on MO3.13, a human oligodendroglioma cell line in order to determine the potential role of Klotho as a tumor suppressor. We show that exogenous Klotho affects the ERK and Akt signaling pathways and decreases the proliferative abilities of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80% of the differentially expressed genes being downregulated. Using gene set enrichment analysis we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain malignancies.

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Chen CD, Li H, Liang J, Hixson K, Zeldich E, Abraham CR