Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

Sun, Fei; Ding, Wen; He, Jianxing; Wang, Xiaojing; Ma, Zhilei; Li, Yanfang

doi:10.1186/s12885-015-1723-x

Cited by 27 publications

(19 citation statements)

References 20 publications

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“…The main factors responsible for this phenomenon are the biological characteristics of metastasis and recurrence in HCC. 15 – 20 Tumorigenesis results from multifactorial, multistep, multigene, and multi-mutation elements. It would be beneficial to, first, discover new biomarkers involved in HCC oncogenesis and progress that predict early tumor recurrence, then clarify their molecular mechanisms, and design better targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT

Huang

Chen

Lin

et al. 2017

OTT

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Stomatin-like protein 2 (SLP-2) gene was significantly upregulated in a variety of tumor tissues and found to be involved in proliferation and metastasis. However, its functional role in hepatocellular carcinoma (HCC) remains unknown. Our study was to investigate the function of SLP-2 in cell proliferation, migration, invasion, cell apoptosis, and the process of epithelial–mesenchymal transition (EMT) in HCC. SLP-2 mRNA and protein expression in HCC were assessed by qRT-PCR and immunohistochemical staining. In vitro, we determined cell proliferation, migration, invasion, and cell apoptosis by CCK-8, transwell, and flow cytometry assays, respectively. SLP-2 was found to be upregulated at both mRNA and protein levels in HCC tissues, and its aberrant overexpression was linked with poor prognosis in patients with HCC. SLP-2 downregulation by siRNAs significantly suppressed cell proliferation, migration, invasion, anti-apoptosis abilities, and inhibited EMT process in vitro. In conclusion, the present study demonstrated the overexpression of SLP-2 in HCC tissues for the first time. As an effective regulator involved in cell proliferation, migration, invasion, cell apoptosis, and EMT, SLP-2 could be a novel therapeutic target for patients with HCC who express high levels of SLP-2.

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Section: Discussionmentioning

confidence: 99%

Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT

Huang

Chen

Lin

et al. 2017

OTT

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“…5A). In these top 20 terms, ranking of prey genes that overlapped with STOML2 was: DTYMK (16 out of 20), PHB (14), PRSS2 (9), PHB2 (8), ATP5B (6), CD8a (2), TCF7L2 (2), GLP1 (1), GLP1R (1). Terms such as "cell cycle", "pyrimidine metabolism", "RNA polymerase", "DNA replication", "mismatch repair", "homologous recombination", were shared between DTYMK/PHB and STOML2 in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways ( Fig.…”

Section: Yeast Two-hybrid Assay Explored Potential Targets Of Stoml2mentioning

confidence: 99%

“…Stomatin-like 2 (aka STOML2, SLP2), which is encoded by gene located on chromosome 9p13, had been initially cloned and identi ed as a novel member of stomatin family in human erythrocytes, lacking NH2terminal hydrophobic domain [6]. Under physiological condition, STOML2 was identi ed within inner mitochondria membrane and faces the intermembrane space, interacted with certain component of the inner mitochondria membrane, and served as a regulator of biogenesis and the activity of mitochondria [7,8] Since Zhang et al discovered the elevation of STOML2 in human esophageal squamous cell carcinoma in 2006 [9], researchers in the recent decade have successively discovered STOML2 as an overexpressed biomarker implicated poor prognosis in pan-cancers, such as endometrial adenocarcinoma [10], glioma cells [11], papillary thyroid cancer [12], cervical cancer [13], epithelial ovarian cancer [14,15], colorectal cancer [16,17], liver cancer [18], head and neck squamous cell carcinoma [19], etc. Additionally, our research team had previously discovered the elevated expression and association with poor prognosis of STOML2 in gastric cancer [20], and furthermore revealed a positive feedback loop of STOML2 to promote gastric cancer progression [21].…”

Section: Introductionmentioning

confidence: 99%

STOML2 Interacts with PHB through Activating MAPK Signaling Pathway to Promote Colorectal Cancer Proliferation.

Chen

et al. 2020

Preprint

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BackgroundOverexpression of STOML2 has been widely reported in a variety of cancer, yet few has detailed its function and regulatory mechanism. This study aims to reveal the clinicopathologic significance and oncologic function of STOML2 in colorectal cancer, explore its specific mechanism by means of yeast two-hybrid assay and bioinformatics.MethodsExpression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay was conducted to screen interacting proteins of STOML2, followed by bioinformatics to predict biological process and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib.ResultsSTOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, ERK1/2 and ELK1 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation.ConclusionsThis study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.

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“…In 2006, a cDNA microarray that revealed the elevation of SLP2 in human esophageal squamous cell carcinoma 13 opened an era to investigate its role in various types of cancer. Successively, it is reported that SLP2 was up-regulated in endometrial adenocarcinoma 14 , glioma cells 15 , papillary thyroid cancer 16 , cervical cancer 17 , epithelial ovarian cancer 18 and rectal cancer 19 . In addition, we previously revealed that the expression of SLP2 was elevated in GC and associated with poor prognosis 5 .…”

Section: Introductionmentioning

confidence: 99%

A Positive Feedback Loop of SLP2 Activates MAPK Signaling Pathway to Promote Gastric Cancer Progression

Wang

et al. 2018

Theranostics

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Rationale: This study is to validate the clinicopathologic significance and potential prognostic value of SLP2 in gastric cancer (GC), to investigate the biological function and regulation mechanism of SLP2, and to explore potential therapeutic strategies for GC.Methods: The expression of SLP2 in GC tissues from two cohorts was examined by IHC. The biological function and regulation mechanism of SLP2 and PHB was validated via loss-of-function or gain-of-function experiments. In vitro proliferation detection was used to evaluate the therapeutic effects of Sorafenib.Results: We validated that SLP2 was significantly elevated in GC tissues and its elevation was associated with poor prognosis of patients. Loss of SLP2 drastically suppressed the proliferation of GC cells and inhibited the tumor growth, while SLP2 overexpression promoted the progression of GC. Mechanistically, SLP2 competed against E3 ubiquitin ligase SKP2 to bind with PHB and stabilized its expression. Loss of SLP2 significantly suppressed phosphorylation of Raf1, MEK1/2, ERK1/2 and ELK1. Furthermore, phosphorylated ELK1 could in turn activate transcription of SLP2. Finally, we demonstrated that a Raf1 inhibitor, Sorafenib, was sufficient to inhibit the proliferation of GC cells.Conclusion: Our findings demonstrated a positive feedback loop of SLP2 which leads to acceleration of tumor progression and poor survival of GC patients. This finding also provided evidence for the reason of SLP2 elevation. Moreover, we found that sorafenib might be a potential therapeutic drug for GC and disrupting the interaction between SLP2 and PHB might also serve as a potential therapeutic target in GC.

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Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

Cited by 27 publications

References 20 publications

Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT

Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT

STOML2 Interacts with PHB through Activating MAPK Signaling Pathway to Promote Colorectal Cancer Proliferation.

A Positive Feedback Loop of SLP2 Activates MAPK Signaling Pathway to Promote Gastric Cancer Progression

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