scholarly journals ZC3H15 promotes glioblastoma progression through regulating EGFR stability

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jianbing Hou ◽  
Minghao Xu ◽  
Hongyu Gu ◽  
Dakun Pei ◽  
Yudong Liu ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Biological Significance ◽  
Protein Stabilization ◽  
Migration And Invasion ◽  
Egfr Signaling ◽  
Inhibitory Effects ◽  
Poor Survival ◽  
Cellular Processes ◽  
Egfr Signaling Pathway

AbstractZinc finger CCCH-type containing 15 (ZC3H15), a highly conserved protein involved in several cellular processes, which was responsible for tumorigenesis and may be a promising marker in myeloid leukemia (AML) and hepatocellular carcinoma (HCC). However, little is known about the biological significance and molecular mechanisms of ZC3H15 in GBM. In this study, we revealed that ZC3H15 was overexpressed in GBM and high ZC3H15 expression was associated with poor survival of patients with GBM. We found that ZC3H15 promoted the proliferation, migration, invasion, and tumorigenesis of GBM cells by activating the EGFR signaling pathway. We also revealed that ZC3H15 reduced EGFR ubiquitination, which was responsible for EGFR protein stabilization. In addition, we demonstrated that ZC3H15 inhibited the transcription of CBL, which was an E3 ubiquitin ligase for EGFR proteasomal degradation. And silencing of CBL could partly abrogate the inhibitory effects on cell proliferation, migration, and invasion of GBM cells induced by ZC3H15 knockdown. Thus, our research revealed the important roles of ZC3H15 in GBM development and provided a brand-new insight for improving the treatment of GBMs.

scholarly journals Trophoblast proliferation, migration, and invasion is regulated by the miR-195/EGFR signaling pathway in recurrent spontaneous abortion patients

2019 ◽  
Author(s):  
Xue Bai ◽  
Chunyang Zheng ◽  
Na Ren
Keyword(s):  
Signaling Pathway ◽  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Egfr Signaling ◽  
Trophoblast Cells ◽  
Egfr Signaling Pathway

ABSTRACTOBJECTIVETo investigate the effect of the miR-195/EGFR signaling pathway on trophoblasts in patients with recurrent spontaneous abortion, thus providing a clinical basis for the diagnosis and treatment of recurrent spontaneous abortion.METHODSRT-qPCR, western blot, flow cytometry, CCK8, cell scratch assay, transwell, and a dual Luciferase reporter assay were used to detect changes in the miR-195/EGFR signaling pathways in clinical samples and in vitro cultured cells and to explore how these changes affect trophoblasts in affected patients.RESULTSExpression of miR-195 was elevated in villus tissues of patients with recurrent spontaneous abortion, while the expression levels of EGFR and its downstream genes p38 and AKT phosphorylation were down-regulated. In vitro cultured cell experiments showed that miR-195 inhibited the proliferation, migration, and invasion of trophoblast cells. EGFR is a target gene of miR-195, and miR-195 suppresses the expression of EGFR.ConclusionThe miR-195/EGFR signaling pathway regulates the proliferation, migration, and invasion of trophoblast cells, thus playing an important role in recurrent spontaneous abortion.

scholarly journals MiR-454-3p and miR-374b-5p suppress migration and invasion of bladder cancer cells through targetting ZEB2

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Suogang Wang ◽  
Geng Zhang ◽  
Wanxiang Zheng ◽  
Qin Xue ◽  
Di Wei ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Inhibitory Effects ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Invasion And Migration ◽  
And Migration

Bladder cancer (BCa) threatens human health due to the high occurrence and mortality. Nowadays, more and more researchers focussed on the molecular mechanisms and biological functions of miRNAs in human cancers. The present study aims to study the biological role of miR-454-3p and miR-374b-5p in BCa. The expression levels of miR-454-3p and miR-374b-5p were detected in BCa tissues and cell lines by qRT-PCR analysis. Kaplan–Meier analysis revealed that the expression levels of miR-454-3p and miR-374b-5p were positively correlated with the overall survival (OS) rate of BCa patients. Gain-of-function assays were conducted to demonstrate the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion, migration, and epithelial–mesenchymal transition (EMT) of BCa cells. Mechanically, ZEB2 was found to be a target of both miR-454-3p and miR-374b-5p. Rescue assays revealed that ZEB2 reversed the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion and migration of BCa cell lines. In summary, miR-454-3p and miR-374b-5p negatively regulated invasion and migration of BCa cell lines via targetting ZEB2.

Role of EGFL7/EGFR-signaling pathway in migration and invasion of growth hormone-producing pituitary adenomas

2018 ◽  
Vol 61 (8) ◽  
pp. 893-901 ◽  
Author(s):  
Qian Liu ◽  
Junwen Zhang ◽  
Hua Gao ◽  
Taoyang Yuan ◽  
Jie Kang ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Signaling Pathway ◽  
Pituitary Adenomas ◽  
Migration And Invasion ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway

scholarly journals DRAM1 plays a tumor suppressor role in NSCLC cells by promoting lysosomal degradation of EGFR

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Ji Geng ◽  
Rong Zhang ◽  
Xiao Yuan ◽  
Haidong Xu ◽  
Zhou Zhu ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Migration And Invasion ◽  
Egfr Signaling ◽  
Lysosomal Degradation ◽  
Cell Lung Carcinoma ◽  
Lung Cancers ◽  
Lysosomal Ph ◽  
Egfr Signaling Pathway

Abstract Lung cancer is the leading cause of cancer-associated mortality worldwide. DNA damage-regulated autophagy modulator 1 (DRAM1) plays an important roles in autophagy and tumor progression. However, the mechanisms by which DRAM1 inhibits tumor growth are not fully understood. Here, we report that DRAM1 was decreased in nonsmall-cell lung carcinoma (NSCLC) and was associated with poor prognosis. We confirmed that DRAM1 inhibited the growth, migration, and invasion of NSCLC cells in vitro. Furthermore, overexpression of DRAM1 suppressed xenografted NSCLC tumors in vivo. DRAM1 increased EGFR endocytosis and lysosomal degradation, downregulating EGFR signaling pathway. On one side, DRAM1 interacted with EPS15 to promote EGFR endocytosis, as evidence by the results of proximity labeling followed by proteomics; on the other, DRAM1 recruited V-ATP6V1 subunit to lysosomes, thereby increasing the assemble of the V-ATPase complex, resulting in decreased lysosomal pH and increased activation of lysosomal proteases. These two actions of DRAM1 results in acceleration of EGFR degradation. In summary, these in vitro and in vivo studies uncover a novel mechanism through which DRAM1 suppresses oncogenic properties of NSCLC by regulating EGFR trafficking and degradation and highlights the potential value of DRAM1 as a prognostic biomarker in lung cancers.

scholarly journals Prognostic and Biological Significance of MicroRNA-127 Expression in Human Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Shaohua Wang ◽  
Hanjun Li ◽  
Jingjie Wang ◽  
Dan Wang ◽  
Anlong Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Multivariate Analyses ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Biological Significance ◽  
Migration And Invasion ◽  
Advanced Clinical Stage ◽  
Reverse Transcription Pcr ◽  
Potential Biomarker

The purpose of this study was to determine the expression of miR-127 and analyze its prognostic and biological significance in breast cancer (BC). A quantitative reverse transcription PCR assay was performed to detect the expression of miR-127 in 15 pairs of BC and corresponding noncancerous tissues. The expression of miR-127 was detected in another 110 BC tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of miR-127 expression. The effects of miR-127 expression on malignant phenotypes of BC cells and its possible molecular mechanisms were further determined. miR-127 was significantly downregulated in BC tissues, and low miR-127 expression was significantly correlated with lymph node metastasis and advanced clinical stage. Patients with low miR-127 showed poorer overall survival than those with high miR-127. Multivariate analyses indicated that status of miR-127 was an independent prognostic factor for patients. Functional analyses showed that upregulation of miR-127 significantly inhibited growth, enhanced apoptosis, and reduced migration and invasion in BC cells by targeting the protooncogene BCL-6. Therefore, miR-127 may be a potential biomarker for predicting the survival of BC patients and might be a molecular target for treatment of human BCs.

scholarly journals A NUMB–EFA6B–ARF6 recycling route controls apically restricted cell protrusions and mesenchymal motility

2018 ◽  
Vol 217 (9) ◽  
pp. 3161-3182 ◽  
Author(s):  
Martina Zobel ◽  
Andrea Disanza ◽  
Francesca Senic-Matuglia ◽  
Michel Franco ◽  
Ivan Nicola Colaluca ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Migration And Invasion ◽  
Nucleotide Exchange ◽  
Cellular Processes ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Endocytic Protein ◽  
Membrane Protrusions

The endocytic protein NUMB has been implicated in the control of various polarized cellular processes, including the acquisition of mesenchymal migratory traits through molecular mechanisms that have only been partially defined. Here, we report that NUMB is a negative regulator of a specialized set of understudied, apically restricted, actin-based protrusions, the circular dorsal ruffles (CDRs), induced by either PDGF or HGF stimulation. Through its PTB domain, NUMB binds directly to an N-terminal NPLF motif of the ARF6 guanine nucleotide exchange factor, EFA6B, and promotes its exchange activity in vitro. In cells, a NUMB–EFA6B–ARF6 axis regulates the recycling of the actin regulatory cargo RAC1 and is critical for the formation of CDRs that mark the acquisition of a mesenchymal mode of motility. Consistently, loss of NUMB promotes HGF-induced cell migration and invasion. Thus, NUMB negatively controls membrane protrusions and the acquisition of mesenchymal migratory traits by modulating EFA6B–ARF6 activity.

Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia and recent therapeutic strategies to overcome resistance

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 461-476 ◽  
Author(s):  
Dale Bixby ◽  
Moshe Talpaz
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Enzyme Inhibitors ◽  
Chronic Phase ◽  
Imatinib Resistance ◽  
Durable Response ◽  
Secondary Resistance ◽  
Cellular Processes

AbstractGiven its relative rarity, it may at first seem surprising that chronic myeloid leukemia (CML) has garnered so much attention over the last decade. Yet, the advances in molecular pathogenesis that have been derived from studying this leukemia have clearly benefited all of oncology. Moreover, the strides in drug design and development that have also ensued around CML have given rise to what others have called a molecular revolution in cancer therapy. While a majority of patients with chronic phase CML (CP-CML) have an excellent durable response to imatinib (Gleevec, Novartis, Basel, Switzerland), a clear minority will unfortunately have signs of primary or secondary resistance to therapy. Significant efforts geared toward understanding the molecular mechanisms of imatinib resistance have yielded valuable insights into the biology of drug trafficking into and out of cells, epigenetic control of cellular processes, alterations in enzymatic structures, and the rational structural-based design of small molecule enzyme inhibitors. This review will describe the efforts at understanding the pathogenesis of imatinib resistance and the molecular rationale for the development of second- and now third-generation therapies for patients with CML.

Triptolide inhibits pituitary adenoma cell viability, migration and invasion via ADAM12/EGFR signaling pathway

Life Sciences ◽  
2018 ◽  
Vol 194 ◽  
pp. 150-156 ◽  
Author(s):  
Junwen Wang ◽  
Zhuo Zhang ◽  
Ran Li ◽  
Wei Sun ◽  
Juan Chen ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Migration And Invasion ◽  
Egfr Signaling ◽  
Adenoma Cell ◽  
Egfr Signaling Pathway

scholarly journals Decorin Suppresses Invasion and EMT Phenotype of Glioma by Inducing Autophagy via c-Met/Akt/mTOR Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanfei Jia ◽  
Qian Feng ◽  
Bo Tang ◽  
Xiaodong Luo ◽  
Qiang Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Xenograft Model ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Mice Model ◽  
Inhibitory Effects ◽  
Poor Survival ◽  
Mouse Xenograft Model ◽  
Epithelial Marker

Decorin exhibits inhibitory effects in tumorigenesis in various types of cancers. The clinical characteristics of 42 patients with GBM were reviewed and analyzed. Lentiviral constructs for decorin overexpression and shRNA-mediated silencing were established for U87MG cells and T98G cells, respectively. The expressions of EMT- and autophagy-associated markers were detected in GBM cell lines. The migration and invasion of the glioma cells were assayed to reflect the malignant behavior of GBM. A mouse xenograft model was used to verify the effect of decorin on autophagy in vivo. Reduced expression of decorin in glioma tissues was associated with a poor survival of the patients. Decorin overexpression suppressed cell migration, invasion and attenuated EMT phenotype in glioma cell lines. Further study indicated that decorin inhibited EMT phenotype through the induction of autophagy. The mechanisms include inhibiting the activation of c-Met/Akt/mTOR signaling and regulating the expressions of mesenchymal markers including Slug, vimentin and Twist, and epithelial marker E-cadherin. In addition, decorin overexpression in a mice model can also suppress the GBM invasion and EMT phenotype. In conclusion, decorin suppresses invasion and EMT phenotype of glioma by inducing autophagy via c-Met/Akt/mTOR axis.

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