High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas

Zhang, Wei; Hong, Tao; Xiao, Chen; Sugimura, Haruhiko; Wang, Jiandong; Zhou, Ping

doi:10.1111/pin.12508

Cited by 9 publications

(10 citation statements)

References 26 publications

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“…This can be used as a new landmark for the prognosis of gastric cancer. 42 The effects of these 10 key genes on EC have not been found, but our analysis shows that it plays B, Enrichment analysis of KEGG pathway as module gene. The color of the bubble represents the significance and the size represents the number of genes involved in the entry.…”

Section: Meg3mentioning

confidence: 74%

Estrogen receptor alpha activates MAPK signaling pathway to promote the development of endometrial cancer

Zhang²,

Yang³

et al. 2019

J of Cellular Biochemistry

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Endometrial cancer (EC) is a common malignant tumor of the female reproductive system in the world. For most of the treated patients, although the survival rate is improved, most patients still have a poor prognosis. The pathogenesis of EC has always been a strong scientific focus, but there is no clear conclusion. Therefore, in view of modularization, this study is to conduct an in‐depth analysis on the effects of estrogen receptor alpha (ERα) regarding EC. The purpose is to identify the molecular course of EC. We obtained 10 co‐expression modules, in which ANO2, EMP3, and other genes are significantly differentially expressed in patients with EC. Additionally, there are active regulatory effects in dysfunction modules, thus genes such as ANO2 and EMP3 would be identified as key genes, which are associated with the development of EC. Enrichment results showed that the module genes were significantly involved in RNA splicing, covalent chromatin modification, histone modification, and organelle fission, and other biological processes, as well as significantly regulated mitogen‐activated protein kinases (MAPK) signaling pathway, Endocytosis, Rap1 signaling pathway, and viral carcinogenesis, and other signaling pathways. Finally, we identified noncoding RNA pivot including FENDRR, miR‐520c‐3p. Besides, transcription factors pivot including NFKB1, E2F1, and RELA which significantly regulate dysfunction module genes. Overall, our work deciphered a co‐expression network involving differential gene regulation in ERα‐associated EC. It helps reveal the core modules and potential regulatory factors of the diseases and enhances our understanding of the pathogenesis. More importantly, we revealed that ERα activates the MAPK signaling pathway to promote the development of EC. It helps to provide a new reference for later research.

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Section: Meg3mentioning

confidence: 74%

Estrogen receptor alpha activates MAPK signaling pathway to promote the development of endometrial cancer

Zhang²,

Yang³

et al. 2019

J of Cellular Biochemistry

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“…Wls protein was expressed in most of the ICC tissues tested (81.8%, score 2+ and 3+). Wls has been reported to be involved in the development of certain human cancers (Maruyama et al 2013;Lu et al 2015;Stewart et al 2015;Zhang et al 2017). Wls is overexpressed in malignant astrocytomas and promotes downstream Wnt signaling (Augustin et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Their data indicated that high CXCR4 expression is associated with ICC progression and metastasis via the canonical Wnt pathway. In previous studies, we investigated Wls expression and its clinical significance in gastric cancer and colorectal cancer and showed that Wls protein was differentially expressed in gastric cancer cell lines and tissue samples (Zhang et al 2017). High expression of Wls in gastric cancer was positively associated with well-differentiated tumor, lymph node metastasis, and advanced TNM stage.…”

Section: Introductionmentioning

confidence: 99%

Wntless Is Highly Expressed in Advanced-Stage Intrahepatic Cholangiocarcinoma

Shi

Bai

Guo

et al. 2018

Tohoku J. Exp. Med.

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Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile duct, representing the second most common primary liver cancer. Wntless (Wls) is a highly conserved transmembrane protein that shuttles palmitoylated Wnt proteins from the endoplasmic reticulum to the plasma membrane. Wls is highly expressed in various types of cancers and is essential for cell proliferation, anti-apoptotic activity, and survival. The profile of Wls expression and its clinical significance has not been well clarified in ICC. In the present study, we analyzed Wls expression in a set of ICC tissues (n = 44) by immunohistochemistry and the relationship between Wls expression and clinicopathological parameters. Immunoreactive Wls was detected in normal cholangiocytes, but was undetectable in normal hepatocytes. The intensity for immunoreactive Wls was varied, depending on ICC specimens. The degree of Wls expression was scored as 0 or 1+ in 8 specimens (18.2%), 2+ in 24 (54.5%), and 3+ in 12 (27.3%) out of the 44 ICC specimens, based on the staining intensity and percentage of Wls-positive cells. In normal cholangiocytes, the scores were varied from 0 to 2+. The intensity of Wls expression was positively associated with tumor stage (T stage, P = 0.005, r = 0.413), tumor-node-metastasis stage (TNM stage, P = 0.000, r = 0.548), and lymphatic invasion (P = 0.000, r = 0.548). Our results show that Wls is differentially expressed in ICC tissues and positively related to tumor stage and lymphatic invasion. Wls is a potential marker for advanced tumor stage and metastasis in ICC.

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“…Dysregulation of WNT processing can trigger UPR in cancer cells and by participating in WNT secretion, GPR177 mitigates ER stress. Aside from important roles in tissue development, GPR177 has been implicated in tumor initiation in several cancers . Although exact mechanisms of GPR177 action in cancer progression require further research, overexpression of GPR177 was previously shown to be positively correlated with cancer development .…”

Section: Discussionmentioning

confidence: 99%

GPR177 promotes gastric cancer proliferation by suppressing endoplasmic reticulum stress‐induced cell death

Seo

Lee

Park

et al. 2018

J of Cellular Biochemistry

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Gastric cancer is the fourth most common cancer worldwide. Despite the high incidence of gastric cancer, efficient chemotherapy treatments still need to be developed. In this study, we examined the anticancer effects of endoplasmic reticulum (ER) stress inducer tunicamycin in gastric cancer. Previously, we found that overexpression of WLS1/GPR177 correlated with poor prognosis in patients with gastric cancer. Furthermore, tunicamycin treatment downregulated GPR177 expression in a dose-dependent manner. GPR177 transports WNT ligand from ER to the plasma membrane, mediating its secretion to the extracellular matrix. In gastric cancer cells, GPR177 preferentially localizes to the ER. Small interfering RNA-mediated knockdown of GPR177 leads to sensitization to ER stress and induces apoptosis of cancer cells along with tunicamycin treatment. GPR177 suppression promoted the ER stress-mediated proapoptotic pathway, such as PERK-CHOP cascade. Furthermore, fluorouracil treatment combined with tunicamycin dramatically reduced cancer cell proliferation. Efficacy of tunicamycin chemotherapy treatments depended on GPR177 expression in gastric cancer cell lines. Together, our results indicate that ER stress can potentiate anticancer effects and suggest GPR177 as a potential gastric cancer therapeutic target.

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High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas

Cited by 9 publications

References 26 publications

Estrogen receptor alpha activates MAPK signaling pathway to promote the development of endometrial cancer

Estrogen receptor alpha activates MAPK signaling pathway to promote the development of endometrial cancer

Wntless Is Highly Expressed in Advanced-Stage Intrahepatic Cholangiocarcinoma

GPR177 promotes gastric cancer proliferation by suppressing endoplasmic reticulum stress‐induced cell death

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