Stanniocalcin1 (STC1) Inhibits Cell Proliferation and Invasion of Cervical Cancer Cells

Guo, Fengjie; Li, Yalin; Wang, Jiajia; Li, Yandong; Li, Yuehui; Li, Guancheng

doi:10.1371/journal.pone.0053989

Cited by 39 publications

(43 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with our tissue findings, STC1 was found to be highly expressed in ccRCC cell lines, with the greatest levels of STC1 expression being observed in metastatic cell lines. These data are consistent with observations reported for the majority of malignancies [ 10 , 22 , 23 , 46 , 47 ], although with the exception of cervical cancer [ 48 ].…”

Section: Discussionsupporting

confidence: 93%

Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma

et al. 2015

J Transl Med

View full text Add to dashboard Cite

BackgroundAlthough metastasis of clear cell renal cell carcinoma (ccRCC) is predominantly observed in late stage tumors, early stage metastasis of ccRCC can also be found with indefinite molecular mechanism, leading to inappropriate clinical decisions and poor prognosis. Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in calcium/phosphate homeostasis, which regulates various cellular processes in normal development and tumorigenesis. This study aimed to investigate the role and mechanism of regulation of STC1 in the metastasis of early stage ccRCC.MethodsSTC1 mRNA and protein expression was determined in ccRCC surgical specimens, RCC cell lines, and human kidney tubule epithelial cell line HKC by real-time polymerase chain reaction (RT-PCR) and western blotting. Immunohistochemistry staining (IHC) and immunofluorescence were also used to examine the expression and localization of STC1 in ccRCC tissues and cancer cells. Knockdown and overexpression studies were conducted in vitro in RCC cell lines using small interfering RNAs (siRNA) and lentiviral-mediated gene delivery to evaluate the role of STC1 in cell proliferation, anchorage-dependent and independent growth, cell cycle control, and migration and invasion.ResultsSTC1 mRNA and protein expression were significantly up-regulated in tumors when compared with non-tumor tissues, with the greatest increase in expression observed in metastatic tissues. Clinicopathological analysis revealed that STC1 mRNA expression was associated with Fuhrman tumor grade (P = 0.008) and overall Tumor Node Metastasis (TNM) staging (P = 0.018). STC1 expression was elevated in T1 stage metastatic tumors when compared with localized tumors, and was positively correlated with average tumor diameter. Silencing of STC1 expression by Caki-1 and A498 resulted in the inhibition of cell proliferation, migration, and invasion, meanwhile down-regulation of STC1 impaired epithelial–mesenchymal transition (EMT) of ccRCC cell lines. Overexpression of STC1 in Caki-2 enhanced cell growth and proliferation but not migration and invasion. Further investigation identified hypoxia and HIF-1α as candidate regulators of STC1 expression.ConclusionsOur findings demonstrate a role for STC1 in metastasis of early stage ccRCC and suggest that STC1 may be a biomarker of potential value both for the prognosis of this disease and for guiding clinical decisions regarding surgical strategies and adjuvant treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0421-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 93%

Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma

et al. 2015

J Transl Med

View full text Add to dashboard Cite

show abstract

“…5C and data not shown). Furthermore, although both wild-type and mutant JMJD3 exhibited similar binding to a previously identified NF-kB p65-binding site at the STC1 promoter (38), H3K27 trimethylation at this location was significantly decreased only in JMJD3wt cells (Fig. 5D).…”

Section: Stc1 a Novel Target Of Jmjd3 Confers Self-renewal Ability supporting

confidence: 52%

H3K27 Demethylase JMJD3 Employs the NF-κB and BMP Signaling Pathways to Modulate the Tumor Microenvironment and Promote Melanoma Progression and Metastasis

et al. 2016

View full text Add to dashboard Cite

Histone methylation is a key epigenetic mark that regulates gene expression. Recently, aberrant histone methylation patterns caused by deregulated histone demethylases have been associated with carcinogenesis. However, the role of histone demethylases, particularly the histone H3 lysine 27 (H3K27) demethylase JMJD3, remains largely uncharacterized in melanoma. Here, we used human melanoma cell lines and a mouse xenograft model to demonstrate a requirement for JMJD3 in melanoma growth and metastasis. Notably, in contrast with previous reports examining T-cell acute lymphoblastic leukemia and hepatoma cells, JMJD3 did not alter the general proliferation rate of melanoma cells in vitro. However, JMJD3 conferred melanoma cells with several malignant features such as enhanced clonogenicity, self-renewal, and transendothelial migration. In addition, JMJD3 enabled melanoma cells not only to create a favorable tumor microenvironment by promoting angiogenesis and macrophage recruitment, but also to activate protumorigenic PI3K signaling upon interaction with stromal components. Mechanistic investigations demonstrated that JMJD3 transcriptionally upregulated several targets of NF-kB and BMP signaling, including stanniocalcin 1 (STC1) and chemokine (C-C motif) ligand 2 (CCL2), which functioned as downstream effectors of JMJD3 in self-renewal and macrophage recruitment, respectively. Furthermore, JMJD3 expression was elevated and positively correlated with that of STC1 and CCL2 in human malignant melanoma. Moreover, we found that BMP4, another JMJD3 target gene, regulated JMJD3 expression via a positive feedback mechanism. Our findings reveal a novel epigenetic mechanism by which JMJD3 promotes melanoma progression and metastasis, and suggest JMJD3 as a potential target for melanoma treatment.

show abstract

“…STC-1 is involved with various biological events such as cell proliferation, migration, invasion, apoptosis, and inflammation in colon, gastric, and cervical cancer (14,16,31,32). In a recent study, we reported that the motility of TNBC cells such as invasion and migration was higher than these abilities in non-TNBC cells through TGF-β1 and -β2 expression (33).…”

Section: Discussionmentioning

confidence: 99%

Elevated STC-1 augments the invasiveness of triple-negative breast cancer cells through activation of the JNK/c-Jun signaling pathway

et al. 2016

View full text Add to dashboard Cite

Stanniocalcin‑1 (STC‑1), a secreted glycoprotein, is highly expressed in a variety of human malignancies. However, the role of STC‑1 has not been fully elucidated in breast cancer cells. Here, we investigated whether STC‑1 acts as a prognostic factor in triple‑negative breast cancer (TNBC) patients, and we explored the cellular mechanism in breast cancer cells. The level of STC‑1 expression was directly associated with the relapse‑free and overall survival of basal‑type breast cancer patients. Breast cancer patients with a high level of STC‑1 had poor prognosis. In addition, our results showed that the level of STC‑1 expression was markedly higher in TNBC than in non‑TNBC cells. Invasiveness of the TNBC cells was also significantly increased in response to recombinant human STC‑1 treatment. In contrast, the invaded cell numbers were completely decreased by STC‑1 siRNA overexpression in the Hs578T and MDA‑MB‑231 TNBC cells. Our results showed that the phosphorylation of c‑Jun N‑terminal protein kinase (JNK) and c‑Jun was increased after STC‑1 treatment but not the phosphorylation of ERK and p38 MAPKs in the Hs578T and MDA‑MB‑231 TNBC cells. Furthermore, expression of one invasion‑related gene MMP‑9, was increased by STC‑1 treatment. STC‑1‑induced MMP‑9 expression was suppressed by SP600125 (a JNK inhibitor) in the Hs578T cells. STC‑1‑induced cell invasiveness was also inhibited by SP600125. Taken together, we demonstrated that aberrant STC‑1 expression is associated with poor prognosis and stimulates the invasiveness of TNBC cells through the JNK/c‑Jun‑dependent signaling pathway.

show abstract

Stanniocalcin1 (STC1) Inhibits Cell Proliferation and Invasion of Cervical Cancer Cells

Cited by 39 publications

References 28 publications

Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma

Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma

H3K27 Demethylase JMJD3 Employs the NF-κB and BMP Signaling Pathways to Modulate the Tumor Microenvironment and Promote Melanoma Progression and Metastasis

Elevated STC-1 augments the invasiveness of triple-negative breast cancer cells through activation of the JNK/c-Jun signaling pathway

Contact Info

Product

Resources

About