GINS2 facilitates epithelial‐to‐mesenchymal transition in non‐small‐cell lung cancer through modulating PI3K/Akt and MEK/ERK signaling
Autor: | Shuguang Zhang, Wenya Li, Xiangli Liu, Lei Sun, Song Zhang |
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Rok vydání: | 2019 |
Předmět: |
Adult
Male 0301 basic medicine MAPK/ERK pathway Epithelial-Mesenchymal Transition Lung Neoplasms Chromosomal Proteins Non-Histone MAP Kinase Signaling System Physiology Clinical Biochemistry Mice Nude Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Western blot Carcinoma Non-Small-Cell Lung medicine Animals Humans Epithelial–mesenchymal transition Protein kinase A Protein kinase B PI3K/AKT/mTOR pathway Aged medicine.diagnostic_test Chemistry Kinase Cell growth Cell Biology Middle Aged 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Heterografts Female Proto-Oncogene Proteins c-akt |
Zdroj: | Journal of Cellular Physiology. 235:7747-7756 |
ISSN: | 1097-4652 0021-9541 |
Popis: | Non-small-cell lung cancer (NSCLC) is a cancer with high morbidity and mortality. We aimed to define the effect of Go-Ichi-Ni-San complex subuint 2 (GINS2) acting on NSCLC. The expressions of GINS2 in NSCLC tissues and cells were detected using real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry (IHC). The relationship between GINS2 expression and NSCLC prognosis or clinicopathologic features was analyzed through statistical analysis. The overexpressed or downexpressed plasmids of GINS2 were transfected into NSCLC cell lines, and then cell proliferation, invasion, and migration viability were, respectively, determined by Cell Counting Kit-8 assay, transwell, and wound healing assay. The epithelial-mesenchymal transition (EMT) was observed and the EMT-related proteins were measured using IHC and western blot. The function of GINS2 in vivo was assessed by mice model. The related proteins of mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were evaluated using western blot. GINS2 expression was upregulated in NSCLC tissues and cell lines, and its high expression was correlated with the poor prognosis and several clinicopathologic features, such as TMN stages (tumor size, lymph node, and metastasis) and clinical stages. GINS2 enhanced NSCLC cell proliferation, migration, and invasion viability in vivo and in vitro. GINS2 also promoted NSCLC cells EMT. In addition, GINS2 could regulate phosphorylated proteins of PI3K p85, Akt, MEK, and ERK expressions, it revealed that GINS2 effected on PI3K/Akt and MEK/ERK pathways. GINS2 promoted cell proliferation, migration, invasion, and EMT via modulating PI3K/Akt and MEK/ERK signaling pathways. It might be a target in NSCLC treatment. |
Databáze: | OpenAIRE |
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