Abstract:Background
Malignant tumours of the female reproductive system threaten the lives and health of women worldwide, with ovarian cancer having the highest mortality rate. Based on previous work, this study analysed the expression and role of YWHAE in ovarian epithelial tumours.
Methods
The interaction between YWHAE and HE4 was evaluated via immunoprecipitation, western blot analysis, and cellular immunofluorescence. Immunohistochemistry was used to ad… Show more
“…Likewise, MACC1 induced β-catenin expression and phosphorylation, an important signaling and adaptor protein in cell–cell junctions ( 169 , 180 , 203 , 215 – 217 ), negatively regulating E-cadherin ( 208 ). As mentioned earlier, MACC1 interacts with YWHAE which was shown to induce lower E-cadherin but higher N-cadherin and vimentin expression ( 186 ), being another explanation for the observed effects. Arguments for MACC1 acting on cell–cell adhesions and cytoskeletal organization are supported by a study in HeLa cells showing lowered actin staining upon MACC1 silencing ( 218 ) and by experiments on glioblastoma cells showing lower equilibrium cell–cell adhesion after MACC1 overexpression ( 13 ).…”
Section: Macc1 In Tumor Migrationmentioning
confidence: 65%
“…Yet, MACC1 may affect PI3K/AKT signaling also via direct interactions with YWHAE (14-3-3 epsilon), as confirmed by affinity capture-MS ( 185 ). YWHAE was previously found to induce PI3K and AKT activation ( 186 ). Additionally, PTEN was reported to suppress cell–matrix adhesion-associated tumor cell migration by inhibition of FAK ( 187 ) and further induce N-cadherin and suppress E-cadherin ( 188 ), while PI3K/Akt signaling had the opposite effects ( 189 ).…”
Malignant tumors are still a global, heavy health burden. Many tumor types cannot be treated curatively, underlining the need for new treatment targets. In recent years, metastasis associated in colon cancer 1 (MACC1) was identified as a promising biomarker and drug target, as it is promoting tumor migration, initiation, proliferation, and others in a multitude of solid cancers. Here, we will summarize the current knowledge about MACC1-induced tumor cell migration with a special focus on the cytoskeletal and adhesive systems. In addition, a brief overview of several in vitro models used for the analysis of cell migration is given. In this context, we will point to issues with the currently most prevalent models used to study MACC1-dependent migration. Lastly, open questions about MACC1-dependent effects on tumor cell migration will be addressed.
“…Likewise, MACC1 induced β-catenin expression and phosphorylation, an important signaling and adaptor protein in cell–cell junctions ( 169 , 180 , 203 , 215 – 217 ), negatively regulating E-cadherin ( 208 ). As mentioned earlier, MACC1 interacts with YWHAE which was shown to induce lower E-cadherin but higher N-cadherin and vimentin expression ( 186 ), being another explanation for the observed effects. Arguments for MACC1 acting on cell–cell adhesions and cytoskeletal organization are supported by a study in HeLa cells showing lowered actin staining upon MACC1 silencing ( 218 ) and by experiments on glioblastoma cells showing lower equilibrium cell–cell adhesion after MACC1 overexpression ( 13 ).…”
Section: Macc1 In Tumor Migrationmentioning
confidence: 65%
“…Yet, MACC1 may affect PI3K/AKT signaling also via direct interactions with YWHAE (14-3-3 epsilon), as confirmed by affinity capture-MS ( 185 ). YWHAE was previously found to induce PI3K and AKT activation ( 186 ). Additionally, PTEN was reported to suppress cell–matrix adhesion-associated tumor cell migration by inhibition of FAK ( 187 ) and further induce N-cadherin and suppress E-cadherin ( 188 ), while PI3K/Akt signaling had the opposite effects ( 189 ).…”
Malignant tumors are still a global, heavy health burden. Many tumor types cannot be treated curatively, underlining the need for new treatment targets. In recent years, metastasis associated in colon cancer 1 (MACC1) was identified as a promising biomarker and drug target, as it is promoting tumor migration, initiation, proliferation, and others in a multitude of solid cancers. Here, we will summarize the current knowledge about MACC1-induced tumor cell migration with a special focus on the cytoskeletal and adhesive systems. In addition, a brief overview of several in vitro models used for the analysis of cell migration is given. In this context, we will point to issues with the currently most prevalent models used to study MACC1-dependent migration. Lastly, open questions about MACC1-dependent effects on tumor cell migration will be addressed.
“…YWHAE can acts as an HE4-interacting protein that can influence the malignant behavior of OV by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase pathways. 34 YWHAE enhances invasion, migration, and proliferation, and inhibits apoptosis in OV cells. 34 Despite the correlation between YWHAE and YWHAEP1 genes, further studies are needed to elucidate their specific relationships and interactions.…”
Section: Resultsmentioning
confidence: 99%
“… 34 YWHAE enhances invasion, migration, and proliferation, and inhibits apoptosis in OV cells. 34 Despite the correlation between YWHAE and YWHAEP1 genes, further studies are needed to elucidate their specific relationships and interactions. Figure 7 cis -edQTLs in OV subtypes (A) Manhattan plot of the FDR for each A-to-I editing site in cis -edQTL mapping.…”
“…Studies have shown that the PI3K/AKT and MAPK signaling pathways are essential for EOC progression ( 22 , 23 ). We retrieved the downregulated gene sets from the PI3K/AKT and MAPK signaling pathways, and the results of the two gene sets were integrated by drawing a Venn diagram.…”
IntroductionNDC80 kinetochore complex component (NUF2) is upregulated and plays an important role in various human cancers. However, the function and mechanism of NUF2 in epithelial ovarian cancer (EOC) remain unclear.MethodsNUF2 expression was detected in EOC tissues and cell lines. The effects of NUF2 downregulation on cell proliferation, migration and invasion in EOC were analyzed by CCK-8 and Transwell assays. Meanwhile, the effect of NUF2 downregulation on tumor growth in vivo was determined by xenograft tumor models. The mechanisms by which NUF2 regulates EOC progression were detected by RNA sequencing and a series of in vitro assays.ResultsWe showed that NUF2 was significantly upregulated in EOC tissues and cell lines, and high NUF2 expression was associated with FIGO stage, pathological grade and poor EOC prognosis. NUF2 downregulation decreased cell proliferation, migration, invasion and tumor growth in nude mice. RNA sequencing studies showed that NUF2 knockdown inhibited several genes enriched in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase (AKT) and mitogen-activated protein kinase (MAPK) signaling pathways. Erb-B2 receptor tyrosine kinase 3 (ERBB3) was the key factor involved in both of the above pathways. We found that ERBB3 silencing could inhibit EOC progression and repress activation of the PI3K-AKT and MAPK signaling pathways. Furthermore, the exogenous overexpression of ERBB3 partially reversed the inhibitory effects on EOC progression induced by NUF2 downregulation, while LY294002 and PD98059 partially reversed the effects of ERBB3 upregulation.ConclusionThese results showed that NUF2 promotes EOC progression through ERBB3-induced activation of the PI3K-AKT and MAPK signaling axes. These findings suggest that NUF2 might be a potential therapeutic target for EOC.
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