Klotho in Cancer: Potential Diagnostic and Prognostic Applications

Abstract

Klotho proteins, αKlotho, βKlotho, and γKlotho, exert tumor-suppressive activities via the fibroblast growth factor receptors and multiple cell-signaling pathways. There is a growing interest in Klotho proteins as potential diagnostic and prognostic biomarkers for multiple diseases. However, recent advances regarding their roles and potential applications in cancer remain disperse and require an integrated analysis. The present review analyzed research articles published between 2012 and 2022 in the Cochrane and Scopus scientific databases to study the role of Klotho in cancer and their potential as tools for diagnosing specific cancer types, predicting tumor aggressiveness and prognosis. Twenty-six articles were selected, dealing with acute myeloid leukemia and with bladder, breast, colorectal, esophageal, gastric, hepatocellular, ovarian, pancreatic, prostatic, pulmonary, renal, and thyroid cancers. αKlotho was consistently associated with improved prognosis and may be useful in estimating patient survival. A single study reported the use of soluble αKlotho levels in blood serum as a tool to aid the diagnosis of esophageal cancer. γKlotho was associated with increased aggressiveness of bladder, breast, and prostate cancer, and βKlotho showed mixed results. Further clinical development of Klotho-based assays will require careful identification of specific tumor subtypes where Klotho proteins may be most valuable as diagnostic or prognostic tools.

The versatility of klotho protein: insights into its multifaceted functions in health and disease

“…With studies, evolving evidence suggests that Klotho can also exhibit [14] CODEN (CAS-USA): WJCMCF oncogenic effects including promoting tumor growth and progression in some specific cases [23,24]. The properties of Klotho to inhibit cellular proliferation, promotion of apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) promote its role as a tumor-suppressing protein [25,26]. Mechanistically, the suppression of tumor and thus metastasis is primarily due to the modulation of various signaling pathways by Klotho including the transforming growth factorbeta (TGF-β) pathway, insulin-like growth factor 1 (IGF-1) pathway, and Wnt/β-catenin pathway,(24) (25).…”

“…The properties of Klotho to inhibit cellular proliferation, promotion of apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) promote its role as a tumor-suppressing protein [25,26]. Mechanistically, the suppression of tumor and thus metastasis is primarily due to the modulation of various signaling pathways by Klotho including the transforming growth factorbeta (TGF-β) pathway, insulin-like growth factor 1 (IGF-1) pathway, and Wnt/β-catenin pathway,(24) (25). Klotho promotes the proliferation of cancer cells, their survival, and resistance to drugs.…”