Klotho inhibits human follicular thyroid cancer cell growth and promotes apoptosis through regulation of the expression of stanniocalcin-1

Dong, Diansheng; Wang, Qi; Li, Xiaofeng; Liu, Jianjing; Ma, Xiaoying; Xu, Wenrong

doi:10.3892/or.2015.4358

Cited by 31 publications

(23 citation statements)

References 40 publications

(55 reference statements)

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“…Overexpression of Klotho inhibited the proliferation and induced apoptosis of T-cell lymphoma cells. The results are consistent with the studies in lung cancer (7,17). Moreover, it has been reported that soluble Klotho and conditioned medium from Klotho- overexpressing cells could suppress the growth of pancreatic cancer and breast cancer cells (16,26).…”

Section: Discussionsupporting

confidence: 92%

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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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Section: Discussionsupporting

confidence: 92%

“…Accumulating evidence has implicated that Klotho is extensively downregulated in several solid malignancies (6)(7)(8)(9). Klotho was revealed to modulate the activity of several signaling pathways, including the FGF signaling, insulin-like growth factor-1 receptor (IGF-1R) and Wnt pathways (5,(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Other studies employing RNA-Seq detect no or very little thyroid Klotho (a Fragments Per Kilobase Of Exon Per Million Fragments Mapped (FPKM) value of 1.93, which amounts to roughly 2 transcripts per cell) [52,55]. Follicular thyroid carcinoma cells express Klotho in vitro, and Klotho was suggested to inhibit cell proliferation and survival [98]. This observation is consistent with a tumour suppressor function of Klotho.…”

Section: Accepted Manuscriptmentioning

confidence: 73%

Tissue expression and source of circulating αKlotho

Olauson

Mencke

Hillebrands

et al. 2017

Bone

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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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“…Some studies have suggested the anti-apoptosis effect of STC1, such as colorectal cancer [27, 28], breast cancer [19, 29], glioma tumor [11, 30], thyroid cancer [20, 31], ovarian cancer [32, 33] and so on. Others indicated the pro-apoptosis effects.…”

Section: Discussionmentioning

confidence: 99%

STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells

Jiang

Liu

et al. 2017

Oncotarget

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Stanniocalin-1 (STC1) is a secreted glycoprotein hormone and involved in various types of human malignancies. Our previous studies revealed that STC1 inhibited cell proliferation and invasion of cervical cancer cells through NF-κB P65 activation, but the mechanism is poorly understood. In our studies, we found overexpression of STC1 promoted cell apoptosis while silencing of STC1 promoted cell growth of cervical cancer. Phospho-protein profiling and Western blotting results showed the expression of NF-κB related phosphorylation sites including NF-κB P65 (Ser536), IκBα, IKKβ, PI3K, and AKT was altered in STC1-overexpressed cervical cancer cells. Moreover, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA could decrease the protein content of phospho-P65 (Ser536), phospho-IκBα, phospho-AKT and phospho-IKKβ while increasing the level of P65 compared to STC1 overexpression groups in cervical cancer cells. Also, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA elevated the percentage of apoptosis and suppressed the G1/S transition in those cells. Additionally, STC1 level was decreased in cervical cancer, especial in stage II and III. The results of immunohistochemistry for the cervical cancer microarray showed that a lower level of STC1, phospho-PI3K and P65 protein expression in tumor tissues than that in normal tissues, and a higher level of phospho-P65 protein expression in tumor tissues, which is consistent with the results of the Western blotting. These data demonstrated that STC1 can promote cell apoptosis via NF-κB phospho-P65 (Ser536) by PI3K/AKT, IκBα and IKK signaling in cervical cancer cells. Our results offer the first mechanism that explains the link between STC1 and cell apoptosis in cervical cancer.

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Klotho inhibits human follicular thyroid cancer cell growth and promotes apoptosis through regulation of the expression of stanniocalcin-1

Cited by 31 publications

References 40 publications

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

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

Tissue expression and source of circulating αKlotho

STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells

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