Klotho expression in cervical cancer: differential expression in adenocarcinoma and squamous cell carcinoma

Aviel‐Ronen, Sarit; Rubinek, Tami; Zadok, Oranit; Vituri, Aya; Avivi, Camila; Wolf, Ido; Barshack, Iris

doi:10.1136/jclinpath-2015-202929

Cited by 24 publications

(10 citation statements)

References 29 publications

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“…Several reports have identified an association between Klotho expression and cancerous changes. Some reports have shown a reduction in the expression of Klotho in invasive breast cancers or cervical cancers, compared with normal lesions (19,20). Moreover, the expression of Klotho has been observed in carcinoma in situ, but not in invasive carcinoma (20,21).…”

Section: Discussionmentioning

confidence: 98%

Klotho expression is correlated to molecules associated with epithelial‑mesenchymal transition in lung squamous cell carcinoma

et al. 2017

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Abstract. Klotho is known as an anti-aging gene. We previously reported that the expression of Klotho is a postoperative prognostic factor for patients with lung large cell neuroendocrine carcinoma and lung small cell carcinoma. Recently, Klotho was shown to suppress the epithelial-mesenchymal transition (EMT). In the present study, we examined the association between the expression of Klotho and the regulation of EMT in lung squamous cell carcinoma. We immunohistochemically examined the expression of Klotho in patients with lung squamous cell carcinoma who had undergone surgical resection or photodynamic therapy. The immunohistochemical analysis showed that Klotho expression was observed not only in normal bronchial epithelial cells, but also in centrally located early lung cancers, which were all carcinomas in situ and were treated using PDT. However, in lung cancer patients with invasive and or advanced squamous cell carcinoma who had undergone a complete surgical resection, Klotho expression was observed in only 4 patients (13%). To elucidate the associations between the expression of Klotho and the expressions of EMT-related proteins, such as E-cadherin, N-cadherin, vimentin, and Snail, we transiently transfected GFP-Klotho plasmid DNA into the human squamous lung cancer cell line SQ5 and examined the expressions of these proteins of GFP-positive cells after sorting using flow cytometry. In SQ5 cells overexpressing GFP-Klotho, the expression of N-cadherin, which is a mesenchymal marker, was completely inhibited, compared with that in SQ5 cells transfected with the GFP vector. The overexpression of Klotho did not affect the regulation of either other mesenchymal markers (such as vimentin and Snail) or the regulation of an epithelial marker (E-cadherin). We concluded that the expression of Klotho was related to the degree of cancer invasiveness and that Klotho inhibits the expression of N-cadherin and regulates the EMT in lung cancer.

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Section: Discussionmentioning

confidence: 98%

Klotho expression is correlated to molecules associated with epithelial‑mesenchymal transition in lung squamous cell carcinoma

et al. 2017

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“…In addition to the ovaries, the cervix may also express some Klotho. PCR data indicate that Klotho is expressed in cervix and in cervical cell lines [138,139], although some studies were negative [7,140]. At the protein level, however, both endocervix and ectocervix appear to express Klotho protein [138,140].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Tissue expression and source of circulating αKlotho

Olauson

Mencke

Hillebrands

et al. 2017

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αKlotho (Klotho), a type I transmembrane protein and a coreceptor for Fibroblast Growth Factor-23, was initially thought to be expressed only in a limited number of tissues, most importantly the kidney, parathyroid gland and choroid plexus. Emerging data may suggest a more ubiquitous Klotho expression pattern which has prompted reevaluation of the restricted Klotho paradigm. Herein we systematically review the evidence for Klotho expression in various tissues and cell types in humans and other mammals, and discuss potential reasons behind existing conflicting data. Based on current literature and tissue expression atlases, we propose a classification of tissues into high, intermediate and low/absent Klotho expression. The functional relevance of Klotho in organs with low expression levels remain uncertain and there is currently limited data on a role for membrane-bound Klotho outside the kidney. Finally, we review the evidence for the tissue source of soluble Klotho, and conclude that the kidney is likely to be the principal source of circulating Klotho in physiology.

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“…The tumor suppressive function of Klotho has been reported in several human solid malignancies, but less in hematological cancers, especially in lymphoma (16)(17)(18)(19). Lower Klotho expression was detected in T-cell lymphoma tissues whereas high expression level of Klotho was observed in normal lymph (17,20,21).…”

Section: Discussionmentioning

confidence: 96%

Klotho suppresses tumor progression via inhibiting IGF-1R signaling in T-cell lymphoma

et al. 2017

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Klotho is a transmembrane protein and acts as an upstream modulator of insulin-like growth factor-1 receptor (IGF-1R) signaling, which was indicated to be involved in the pathogenesis of solid cancer and hematological malignancies, including T‑cell lymphoma. Although Klotho was recently identified as a tumor suppressor in several types of human malignancies, the potential role of Klotho in T‑cell lymphoma has not been reported. In the present study, we investigated the expression level and the molecular events of Klotho in T‑cell lymphoma. Significantly lower expression of Klotho was observed in T‑cell lymphoma patient samples compared to normal lymph nodes. Functional analysis after Klotho overexpression revealed significantly inhibited tumor cell viability in T‑cell lymphoma. Moreover, apoptosis of T‑cell lymphoma cells were induced after transfected with Klotho-overexpressing vectors. Forced expression of Klotho resulted in decline of activation of IGF-1R signaling, accompanied by decreased phosphorylation of its downstream targets, including AKT and ERK1/2. These data indicated that Klotho acts as a tumor suppressor via inhibiting IGF-1R signaling, thus suppressing the viability and promoting apoptosis in T‑cell lymphoma. Taken together, Klotho may serve as a potential target for the therapeutic intervention of T‑cell lymphoma.

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Klotho expression in cervical cancer: differential expression in adenocarcinoma and squamous cell carcinoma

Cited by 24 publications

References 29 publications

Klotho expression is correlated to molecules associated with epithelial‑mesenchymal transition in lung squamous cell carcinoma

Klotho expression is correlated to molecules associated with epithelial‑mesenchymal transition in lung squamous cell carcinoma

Tissue expression and source of circulating αKlotho

Klotho suppresses tumor progression via inhibiting IGF-1R signaling in T-cell lymphoma

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