Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo

Liu, Ying; Xiao, Haijun; Xue, Feng

doi:10.1590/1678-4685-gmb-2019-0229

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…The association of metastasis with lymph nodes is frequently observed in studies that deal with breast cancer ( 83 , 84 ). Studies have demonstrated the importance of Klotho in inhibiting metastasis in mice ( 26 , 85 ). Due to the results of previous studies, Klotho was expected to have an important function in protecting patients against tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

et al. 2022

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Klotho, a cellular anti-senescence protein, is related to antitumor actions, growth regulation, proliferation and invasiveness in several types of tumor, including breast cancer. The present study aimed to analyze the serum levels of αKlotho in patients with breast cancer according to histopathological and immunohistochemical variables. A total of 74 patients and 60 healthy controls were recruited. Peripheral blood samples were collected and serum levels were assessed by sandwich ELISA. Clinical and diagnostic data were obtained from medical records and databases of the Clinical Hospital of the Federal University of Uberlândia (Uberlândia, Brazil). The results indicated no difference in the levels of αKlotho between patients and controls (P=0.068); however, the number of patients with breast cancer with undetectable αKlotho was high (n=52). Thus, the variables that were associated with the lowest survival rates were analyzed, relating them to undetectable αKlotho. Among cases of metastatic tumors or tumors with poor differentiation, positive lymph node status and triple-negative status, patients with undetectable αKlotho predominated and had unfavorable overall survival. Due to the significant results obtained in triple-negative patients, an in vitro analysis was performed to determine whether estrogen receptors (ERs) have a role in αKlotho production. Treatment of MCF-7 cells with ER agonists, estradiol (E2) and diarylpropionitrile (DPN), resulted in increases in αKlotho expression and supernatant levels of both agonists, demonstrating a direct association between the ER and Klotho production; of note, the ERβ-specific agonist DPN tripled αKlotho expression when compared to E2 (P=0.078). These data suggested that undetectable αKlotho in the serum of patients with breast cancer is related to unfavorable histopathological variables and poor prognosis and ERs possibly have an important role in maintaining adequate quantities of αKlotho.

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Section: Discussionmentioning

confidence: 99%

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

et al. 2022

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“…The positive association between Klotho expression and tumour progression is likely because of Klotho's role in cancer development. Human studies on cervical cancer, 37 osteosarcoma, 38 and renal cell carcinoma 39 have shown that Klotho inhibits cell proliferation, migration and invasion. ALT is a liver‐specific cytosolic enzyme, which is elevated with hepatocellular injury.…”

Section: Discussionmentioning

confidence: 99%

Reduced Klotho expression and its prognostic significance in canine hepatocellular carcinoma

Kim

Chung

Lee

et al. 2022

Vet Comparative Oncology

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Klotho is an anti‐ageing gene and is known to act as a tumour suppressor in human hepatocellular carcinoma (HCC). According to a previous study, Klotho is present in normal canine mammary glands, and down‐expression in tumours is positively associated with negative prognosis. However, the presence and significance of Klotho in canine HCC has not yet been reported. This study aimed to confirm Klotho expression in normal canine liver tissues using western blotting and immunohistochemistry, and whether the expression differed in non‐neoplastic liver disease and HCC. Furthermore, correlation between clinicopathologic features and expression of Klotho was evaluated. All of the normal liver tissues showed the presence of Klotho, and Klotho expression was significantly decreased in the HCC tissue as compared to the non‐neoplastic hepatic tissue. Additionally, Klotho expression was significantly associated with tumour size (P = .045), liver enzyme (alanine aminotransferase (ALT)) (P = .018), and metastasis (P = .024). Analysis of the survival curve revealed that reduced Klotho expression was significantly associated with poor disease‐free survival (P = .041) in HCC. These results show that Klotho expression is present in normal canine liver tissue and that reduced Klotho expression is associated with poor prognosis in canine HCC. Thus, Klotho was presumed to be a potential clinical prognostic marker for canine HCC.

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“…Also, we reported the inverse correlation between the α-Klotho gene expression and the stage of DTC (p = 0.026), as well as the tumor size (p < 0.001). Li and his colleagues [35] had injected the mice with transduced osteosarcoma cells with overexpressed α-Klotho to evaluate the effect of α-Klotho on tumor growth. After 4 weeks, they had found that α-Klotho overexpression significantly diminished the tumor weight and volume in the mice model of osteosarcoma, compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Role of alpha and gamma Klotho genes in the development of differentiated thyroid carcinoma on top of goiter

El-Saeed,

Elnagdy,

Abd elghaffar

et al. 2022

Forum of Clinical Oncology

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Background Differentiated thyroid carcinoma (DTC) is the most common malignant tumor of the endocrine system. Our study is aimed to investigate the role of the α- and γ-Klotho genes in the development and progression of DTC. Methods The expression of the α- and γ-Klotho genes was assessed by quantitative real-time polymerase chain reaction (RT-qPCR) in thyroid tissues of 40 DTC patients and 40 age- and sex-matched subjects diagnosed as goiter and included as a control group. The demographic, laboratory and clinicopathological data of the subjects were reviewed to detect their association with the Klotho genes. Results The α-Klotho gene expression was statistically significantly lower in DTC tissues compared to goiter tissues (p < 0.001). However, there was no statistically significant association between the γ-Klotho gene expression and DTC (p = 0.643). Receiver operating characteristic (ROC) curve analysis showed the diagnostic value of the α-Klotho mRNA levels, by providing an AUC of 0.954 value (95% CI = 0.910–0.999; p < 0.001). Lower α-Klotho gene expression associated significantly with higher stages of DTC (p = 0.026). Logistic regression analysis declared that low α-Klotho mRNA expression was demonstrated to be a significant predictor for the likelihood of DTC on top of goiter (p = 0.001). Conclusions Our study showed the role of the α-Klotho gene as a potential novel biomarker for discrimination between DTC and goiter tissues. Low α-Klotho mRNA expression was found to be a significant predictor for the likelihood of DTC on top of goiter, as well as higher stages of this tumor.

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Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo

Cited by 7 publications

References 28 publications

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

Reduced Klotho expression and its prognostic significance in canine hepatocellular carcinoma

Role of alpha and gamma Klotho genes in the development of differentiated thyroid carcinoma on top of goiter

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