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The role of α-klotho in human cancer: molecular and clinical aspects

Oncogene volume 41, pages 4487–4497 (2022)Cite this article

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Abstract

Klotho is a well-established longevity hormone. Its most prominent function is the regulation of phosphate homeostasis. However, klotho possesses multiple pleiotropic activities, including inhibition of major signaling pathways, reducing oxidative stress and suppressing inflammation. These activities are tightly associated with cancer, and klotho was discovered as a universal tumor suppressor. We review here novel molecular aspects of klotho activity in cancer, focusing on its structure–function relationships and clinical aspects regarding its expression, blood levels, clinical risk, and prognostic value in the clinical setting. In addition, the potential benefit of klotho treatment combined with chemotherapy, biological therapy, or immunotherapy, are discussed. Finally, as klotho was shown in preclinical models to inhibit cancer development and growth, we discuss various approaches to developing klotho-based therapies.

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Fig. 1: Modulation of oncogenic pathways by klotho.
Fig. 2: Protein structure of α-klotho.

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Acknowledgements

The research leading to this work has received funding supported by Tova and Sami Sagol Foundation.

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Authors and Affiliations

  1. Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Hagai Ligumsky, Keren Merenbakh-Lamin, Noa Keren-Khadmy, Ido Wolf & Tami Rubinek

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Hagai Ligumsky, Ido Wolf & Tami Rubinek

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  1. Hagai Ligumsky
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Conceptualization: HL, IW, and TR; literature review: HL, KML, and TR; Protein modeling: NKK; Writing and revising the paper: HL, KML, IW, and TR.

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Correspondence to Tami Rubinek.

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Ligumsky, H., Merenbakh-Lamin, K., Keren-Khadmy, N. et al. The role of α-klotho in human cancer: molecular and clinical aspects. Oncogene 41, 4487–4497 (2022). https://doi.org/10.1038/s41388-022-02440-5

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