Researchers at UT Southwestern Medical Center have found that the anti-aging hormone klotho is able to prevent the spread of cancer and suppress renal fibrosis, a condition that often leads to a need for dialysis or kidney transplantation. The researchers, led by Dr Makoto Kuro-o, the man that discovered klotho, focused their study on mesenchymal cells. These cells are essential for growth and development, however in some circumstances they can morph into a pathological form that causes fibrosis and metastasis in cancer cells. For the study, they blocked a ureter or introduced human cancer cells into mice. Results showed that administration of klotho blocked three signaling pathways that are known to cause fibrosis or cancer metastasis. Further analysis revealed that klotho binds to the mesenchymal cells' transforming growth factor (TGF) receptor and inhibits the signaling needed for epithelial-to-mesenchyma transition (EMT) a cellular switch that causes cells to transform into a more malleable form. It is this transformation that enables cancer cells to metastasize. The researchers said their discoveries "offer real hope for patients with renal disease" and provide "further evidence that Klotho is an understudied tumor-suppressor."
Shigehiro Doi, Yonglong Zou, Osamu Togao, Johanne V. Pastor, George B. John, Lei Wang, et al. Klotho inhibits transforming growth factor-β1 (TGF-β1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 2011;286:8655-8665. DOI:10.1074/jbc.M110.174037
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