High RIN1 expression is associated with poor prognosis in patients with gastric adenocarcinoma

Yu, Haifeng; Zhao, Gang; Zhang, Ge; Wang, Daorong; Chen, Jie; Zhang, Yun; Zha, Tian-Zhou; Zhang, Kai; Zhang, Miao; Tan, Yongfei; Zhou, Shunhua; Jiang, Chao

doi:10.1007/s13277-012-0409-0

Cited by 17 publications

(9 citation statements)

References 20 publications

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“…In so doing, we have uncovered novel functions for PRKCD and RIN1 that, although previously shown to function in receptor trafficking, had no known roles in regulating trafficking of soluble proteins. Of particular interest then is our finding that high expression of the PTPN14 substrates RIN1 and PRKCD correlated with poor patient survival in breast cancer, which concurs with previously published reports that PRKCD negatively correlates with survival in breast cancer patients (41) and RIN1 negatively correlates with survival in melanoma (42), gastric adenocarcinoma (43), bladder urothelial carcinoma (44), and non-small cell lung cancer (45). Recognizing that the trafficking of prometastatic factors and growth factor receptors is inhibited by PTPN14, and that it is promoted by PRKCD and RIN1, our findings reveal potential strategies for simultaneously reducing the mobilization of soluble factors and cell surface receptors that promote tumor cell growth and survival.…”

Section: Discussionsupporting

confidence: 90%

The tyrosine phosphatase PTPN14 (Pez) inhibits metastasis by altering protein trafficking

et al. 2015

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Factors secreted by tumor cells shape the local microenvironment to promote invasion and metastasis, as well as condition the premetastatic niche to enable secondary-site colonization and growth. In addition to this secretome, tumor cells have increased abundance of growth-promoting receptors at the cell surface. We found that the tyrosine phosphatase PTPN14 (also called Pez, which is mutated in various cancers) suppressed metastasis by reducing intracellular protein trafficking through the secretory pathway. Knocking down PTPN14 in tumor cells or injecting the peritoneum of mice with conditioned medium from PTPN14-deficient cell cultures promoted the growth and metastasis of breast cancer xenografts. Loss of catalytically functional PTPN14 increased the secretion of growth factors and cytokines, such as IL-8 (interleukin-8), and increased the abundance of EGFR (epidermal growth factor receptor) at the cell surface of breast cancer cells and of FLT4 (vascular endothelial growth factor receptor 3) at the cell surface of primary lymphatic endothelial cells. We identified RIN1 (Ras and Rab interactor 1) and PRKCD (protein kinase C-δ) as binding partners and substrates of PTPN14. Similar to cells overexpressing PTPN14, receptor trafficking to the cell surface was inhibited in cells that lacked PRKCD or RIN1 or expressed a nonphosphorylatable RIN1 mutant, and cytokine secretion was decreased in cells treated with PRKCD inhibitors. Invasive breast cancer tissue had decreased expression of PTPN14, and patient survival was worse when tumors had increased expression of the genes encoding RIN1 or PRKCD. Thus, PTPN14 prevents metastasis by restricting the trafficking of both soluble and membrane-bound proteins.

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Section: Discussionsupporting

confidence: 90%

The tyrosine phosphatase PTPN14 (Pez) inhibits metastasis by altering protein trafficking

et al. 2015

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“…Although research studies have found that many aberrantly expressed genes in GC can contribute to the malignant behavior, the identification of novel molecular markers is still urgently needed 17,18. The WWC family protein has been implicated in human cancers.…”

Section: Discussionmentioning

confidence: 99%

WWC3 downregulation correlates with poor prognosis and inhibition of Hippo signaling in human gastric cancer

Hou

Zhou

2017

OTT

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The aim of this study was to investigate the clinicopathological significance and biological roles of WWC3 in human gastric cancer (GC). Clinical significance of WWC3 in human GCs was examined by using immunohistochemistry (IHC). WWC3 was downregulated in 48 of 111 human GCs, and its downregulation was associated with advanced stage, positive nodal status, and higher relapse rate. Importantly, WWC3 downregulation correlated with poor survival. It was also found that WWC3 protein expression was downregulated in GC cell lines compared with normal cell line GES-1. On one hand, WWC3 overexpression inhibited the cell growth rate and invading ability in HGC-27 cell line. On the other hand, depleting WWC3 by small interfering RNA (siRNA) promoted proliferation rate and invading ability in the SGC-7901 cell line. In addition, cell cycle analysis showed that WWC3 overexpression inhibited while its depletion accelerated cell cycle progression at the G1/S transition. Western blot (WB) analysis demonstrated that WWC3 repressed cyclin D1 and cyclin E while upregulated p27 expression. Luciferase reporter assay showed that WWC3 activated Hippo signaling pathway by suppressing TEAD transcription activity, with downregulation of total and nuclear YAP and its target CTGF. WWC3 siRNA depletion exhibited the opposite effects. In conclusion, this study indicates that WWC3 serves as a tumor suppressor in GC by activating Hippo signaling.

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“…GGT6 has been linked to immune infiltration and inflammation and putatively to alterations in DNA methylation via changing levels of glutathione and methyl group availability [39,40]. Other CpGs are associated with genes related to immune function, including T cell regulation and inflammation, tumor initiation and angiogenesis (EBI3) [41,42], while other genes have been implicated in cancer aggressiveness (AQP9, RIN1) [43][44][45][46][47].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation profiling reveals novel diagnostic biomarkers in renal cell carcinoma

et al. 2014

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Background: Renal cell carcinoma (RCC) is the tenth most commonly diagnosed cancer in the United States. While it is usually lethal when metastatic, RCC is successfully treated with surgery when tumors are confined to the kidney and have low tumor volume. Because most early stage renal tumors do not result in symptoms, there is a strong need for biomarkers that can be used to detect the presence of the cancer as well as to monitor patients during and after therapy.

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High RIN1 expression is associated with poor prognosis in patients with gastric adenocarcinoma

Cited by 17 publications

References 20 publications

The tyrosine phosphatase PTPN14 (Pez) inhibits metastasis by altering protein trafficking

The tyrosine phosphatase PTPN14 (Pez) inhibits metastasis by altering protein trafficking

WWC3 downregulation correlates with poor prognosis and inhibition of Hippo signaling in human gastric cancer

DNA methylation profiling reveals novel diagnostic biomarkers in renal cell carcinoma

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