Increased levels of SLP-2 correlate with poor prognosis in gastric cancer

Liu, Dongning; Zhang, Lei; Shen, Zhiyong; Tan, Fei; Hu, Yanfeng; Yu, Jiang; Li, Guoxin

doi:10.1007/s10120-013-0232-3

Cited by 26 publications

(31 citation statements)

References 17 publications

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“…IHC detection for WWP1 protein expression Immunohistochemistry (IHC) assay for WWP1 protein expression was performed as described earlier [23][24][25]. In brief, the sections were dewaxed in xylene and rehydrated in graded alcohol according to the standard protocol.…”

Section: Tumor Samplesmentioning

confidence: 99%

WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma

Zhang

et al. 2014

Tumor Biol.

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Whelming evidence has demonstrated that WW domain containing E3 ubiquitin protein ligase 1 (WWP1) participates in a wide variety of biological processes and is tightly related to the initiation and progression of many tumors. Currently, although mounting evidence supports a role of WWP1 in tumor promotion and tumorigenesis, the potential roles of WWP1 and its biological functions in gastric carcinoma are not fully understood. Here, we found that WWP1 messenger RNA (mRNA) and protein were highly expressed in gastric carcinoma tissues and cells. High WWP1 mRNA and protein levels were tightly related to differentiation status, TNM stage, invasive depth, lymph node metastasis, and poor prognosis in gastric carcinoma. Furthermore, WWP1 siRNA significantly decreased WWP1 protein level in MKN-45 and AGS cells; meanwhile, WWP1 depletion markedly inhibited tumor proliferation in vitro and in vivo, arrested cell cycle at G0/G1 phase, and induced cell apoptosis in MKN-45 and AGS cells. Most notably, WWP1 downregulation both inactivated PTEN-Akt signaling pathway in MKN-45 and AGS cells. Taken altogether, our findings suggest that WWP1 acts as an oncogenic factor and should be considered as a novel interfering molecular target for gastric carcinoma.

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Section: Tumor Samplesmentioning

confidence: 99%

WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma

Zhang

et al. 2014

Tumor Biol.

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“…SLP-2 was first identified as a novel cancer-related gene in 2006 and was found to be overexpressed in several types of human tumors, including breast cancer, gastric cancer, colorectal cancer, glioma, laryngeal squamous cell carcinoma (LSCC), esophageal squamous cell carcinoma (ESCC), lung cancer and endometrial adenocarcinoma (14)(15)(16)(17)(18)(19). Inhibition of SLP-2 was found to decrease cell proliferation, adhesion and tumor cell motility (20), suggesting that SLP-2 may play an important role in tumorigenesis.…”

Section: Stomatin-like Protein 2 Is Associated With the Clinicopatholmentioning

confidence: 99%

Stomatin-like protein 2 is associated with the clinicopathological features of human papillary thyroid cancer and is regulated by TGF-β in thyroid cancer cells

Liu

Zhang

et al. 2013

Oncology Reports

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Papillary thyroid cancer (PTC) accounts for 80-90% of all cases of thyroid malignancies. Stomatin-like protein 2 (SLP-2) is a novel member of the stomatin superfamily and is found in several types of human tumors. However, whether it is expressed in human PTC is unknown. In the present study, we aimed to explore the diagnostic value of SLP-2 in patients with PTC and to investigate whether SLP-2 expression is regulated by transforming growth factor-β (TGF-β), a cytokine which plays an important role in PTC tumorigenesis. A total of 107 patients consisting of 99 cases of classical and 8 cases of follicular variant PTC was examined. The expression of SLP-2 mRNA and protein was examined by immunohistochemistry (IHC) and qPCR, respectively. We found that SLP-2 was overexpressed in human PTC. The expression of SLP-2 was significantly associated with clinicopathological features of the PTC cases. Particularly, increased SLP-2 expression was mainly correlated with primary tumors >1 cm in size, with late stage tumors and with metastatic lymph nodes. The expression of SLP-2 was correlated with the expression of Ki-67, a cell proliferation marker, in PTC tissues as detected by IHC. SLP-2 was upregulated by TGF-β1 in PTC cells as evaluated by western blotting. The present data revealed for the first time that patients with PTC exhibited SLP-2 overexpression that was associated with clinicopathological features. The correlation between SLP-2 expression and proliferation marker Ki-67 may be characteristic of PTC and may reflect PTC progression. SLP-2 was upregulated by TGF-β1, indicating a possible role of SLP-2 in PTC tumorigenesis. Our data suggest that SLP-2 may be considered as a useful diagnostic marker and therapeutic target for PTC.

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“…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]. Albeit discovery of STOML2 overexpression in multiple cancers and a handful of tracing to regulatory mechanism were reported, systemic assessment of STMOL2 is still absent.…”

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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Increased levels of SLP-2 correlate with poor prognosis in gastric cancer

Cited by 26 publications

References 17 publications

WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma

WWP1 as a potential tumor oncogene regulates PTEN-Akt signaling pathway in human gastric carcinoma

Stomatin-like protein 2 is associated with the clinicopathological features of human papillary thyroid cancer and is regulated by TGF-β in thyroid cancer cells

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

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