Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis

Shiryaev, Alexey; Ghelue, Marijke Van; Moens, Ugo

doi:10.1007/978-90-481-9522-0_4

Cited by 2 publications

(2 citation statements)

References 228 publications

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“…In recent years, a large number of studies have found that the MAPK pathway, as a highly conserved family of protein kinases, can transmit information from extracellular signals into the nucleus and regulate a variety of biological processes such as cell proliferation, differentiation, migration and apoptosis 11-13. MAPKs are a family of protein kinases that direct cellular response to a variety of stimuli, including mitogens, osmotic pressures, heat shock and proinflammatory cytokines 14. MAPKs are activated in the kinase activation circuit by phosphorylation of threonine and tyrosine residues in the conserved label T-X-Y motif.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13] MAPKs are a family of protein kinases that direct cellular response to a variety of stimuli, including mitogens, osmotic pressures, heat shock and proinflammatory cytokines. 14 MAPKs are activated in the kinase activation circuit by phosphorylation of threonine and tyrosine residues in the conserved label T-X-Y motif. It mainly includes extracellular signal-regulated kinases 1 and 2 (ERK1/2), C-Jun amino-terminal kinase (JNK) and p38.…”

Section: Discussionmentioning

confidence: 99%

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Dual-specificity phosphatase 8 (DUSP8) induces drug resistance in breast cancer by regulating MAPK pathways

Zhang

Wang

Chen

et al. 2022

Journal of Investigative Medicine

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The aim of the study was to explore the role and molecular mechanism of dual-specificity phosphatase 8 (DUSP8) in the drug resistance of trastuzumab in breast cancer. Real-time PCR and western blot detected the difference in expression of DUSP8 between breast cancer tissue/cells and trastuzumab-resistant tissues/cells. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DUSP8 in breast cancer. si-DUSP8 or dusp8 overexpression vector was transiently transfected, and the effects of si-DUSP8 on apoptosis, cell viability and cell migration of drug-resistant cell lines were investigated by flow cytometry, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) and Transwell assays, and its regulation mechanism finally explored. The results showed that the expression of DUSP8 in breast cancer tissues and cells was significantly higher than in matched non-tumor tissues and cells. DUSP8 was significantly upregulated in non-responsive patients compared with patients who responded to trastuzumab. ROC analysis showed that the area under the curve was 0.732, and the diagnostic sensitivity and specificity were 64.86% and 75.76%. DUSP8 knockdown promotes apoptosis and reduces trastuzumab resistance in BT474/TR and SKBR3/TR cells by inhibiting cell migration and cell viability. Knockdown of DUSP8 increased the expression of p-p38 and p-ERK, and the regulation of DUSP8 in chemotherapy resistance of breast cancer cells may be realized by mediating mitogen-activated protein kinase (MAPK)-related signaling pathways. In conclusion, knockdown of DUSP8 expression in trastuzumab-resistant cells can inhibit cell migration and proliferation, and leads to decreased drug resistance by activating MAPK signaling pathway in trastuzumab-resistant cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dual-specificity phosphatase 8 (DUSP8) induces drug resistance in breast cancer by regulating MAPK pathways

Zhang

Wang

Chen

et al. 2022

Journal of Investigative Medicine

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Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

Kostenko

Dumitriu²,

Lægreid³

et al. 2011

WJBC

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Mitogen-activated protein kinases (MAPKs) are a family of proteins that constitute signaling pathways involved in processes that control gene expression, cell division, cell survival, apoptosis, metabolism, differentiation and motility. The MAPK pathways can be divided into conventional and atypical MAPK pathways. The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases, MAPK kinase, and MAPK. Atypical MAPK pathways are not organized into this three-tiered cascade. MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases. The latter are referred to as MAPK-activated protein kinases. This review focuses on one such MAPK-activated protein kinase, MAPK-activated protein kinase 5 (MK5) or p38-regulated/activated protein kinase (PRAK). This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways. Recent findings on the regulation of the activity and subcellular localization, bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

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Mitogen-Activated Protein Kinase-Activated Protein Kinases and Metastasis

Cited by 2 publications

References 228 publications

Dual-specificity phosphatase 8 (DUSP8) induces drug resistance in breast cancer by regulating MAPK pathways

Dual-specificity phosphatase 8 (DUSP8) induces drug resistance in breast cancer by regulating MAPK pathways

Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

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