scholarly journals Extracellular signal-regulated kinases associate with and phosphorylate DHPS to promote cell proliferation

Oncogenesis ◽  
2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Chao Wang ◽  
Zhen Chen ◽  
Litong Nie ◽  
Mengfan Tang ◽  
Xu Feng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Protein Translation ◽  
Deoxyhypusine Synthase ◽  
Promote Cell Proliferation ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Direct Binding ◽  
Kinase Substrates

Abstract The ERK1/2 pathway is one of the most commonly dysregulated pathways in human cancers and controls many vital cellular processes. Although many ERK1/2 kinase substrates have been identified, the diversity of ERK1/2 mediated processes suggests the existence of additional targets. Here, we identified Deoxyhypusine synthase (DHPS), an essential hypusination enzyme regulating protein translation, as a major and direct-binding protein of ERK1/2. Further experiments showed that ERK1/2 phosphorylate DHPS at Ser-233 site. The Ser-233 phosphorylation of DHPS by ERK1/2 is important for its function in cell proliferation. Moreover, we found that higher DHPS expression correlated with poor prognosis in lung adenocarcinoma and increased resistance to inhibitors of the ERK1/2 pathway. In summary, our results suggest that ERK1/2-mediated DHPS phosphorylation is an important mechanism that underlies protein translation and that DHPS expression is a potent biomarker of response to therapies targeting ERK1/2-pathway.

scholarly journals The Role of the Anti-Aging Protein Klotho in IGF-1 Signaling and Reticular Calcium Leak: Impact on the Chemosensitivity of Dedifferentiated Liposarcomas

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 439 ◽  
Author(s):  
Vanessa Delcroix ◽  
Olivier Mauduit ◽  
Nolwenn Tessier ◽  
Anaïs Montillaud ◽  
Tom Lesluyes ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Therapy Resistance ◽  
High Grade ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Well Differentiated

By inhibiting Insulin-Like Growth Factor-1-Receptor (IGF-1R) signaling, Klotho (KL) acts like an aging- and tumor-suppressor. We investigated whether KL impacts the aggressiveness of liposarcomas, in which IGF-1R signaling is frequently upregulated. Indeed, we observed that a higher KL expression in liposarcomas is associated with a better outcome for patients. Moreover, KL is downregulated in dedifferentiated liposarcomas (DDLPS) compared to well-differentiated tumors and adipose tissue. Because DDLPS are high-grade tumors associated with poor prognosis, we examined the potential of KL as a tool for overcoming therapy resistance. First, we confirmed the attenuation of IGF-1-induced calcium (Ca2+)-response and Extracellular signal-Regulated Kinase 1/2 (ERK1/2) phosphorylation in KL-overexpressing human DDLPS cells. KL overexpression also reduced cell proliferation, clonogenicity, and increased apoptosis induced by gemcitabine, thapsigargin, and ABT-737, all of which are counteracted by IGF-1R-dependent signaling and activate Ca2+-dependent endoplasmic reticulum (ER) stress. Then, we monitored cell death and cytosolic Ca2+-responses and demonstrated that KL increases the reticular Ca2+-leakage by maintaining TRPC6 at the ER and opening the translocon. Only the latter is necessary for sensitizing DDLPS cells to reticular stressors. This was associated with ERK1/2 inhibition and could be mimicked with IGF-1R or MEK inhibitors. These observations provide a new therapeutic strategy in the management of DDLPS.

scholarly journals Low expression lncRNA RPLP0P2 is associated with poor prognosis and decreased cell proliferation and adhesion ability in lung adenocarcinoma

2016 ◽  
Vol 36 (3) ◽  
pp. 1665-1671 ◽  
Author(s):  
Jie Chen ◽  
Lijuan Hu ◽  
Jian Chen ◽  
Fang Wu ◽  
Dongwei Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Poor Prognosis ◽  
Adhesion Ability ◽  
Low Expression

scholarly journals Long Noncoding RNA RGMB-AS1 Indicates a Poor Prognosis and Modulates Cell Proliferation, Migration and Invasion in Lung Adenocarcinoma

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150790 ◽  
Author(s):  
Ping Li ◽  
Guojun Zhang ◽  
Juan Li ◽  
Rui Yang ◽  
Shanshan Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
Migration And Invasion

scholarly journals Upregulated INHBA Expression May Promote Cell Proliferation and Is Associated with Poor Survival in Lung Adenocarcinoma

Neoplasia ◽  
2009 ◽  
Vol 11 (4) ◽  
pp. 388-396 ◽  
Author(s):  
Christopher W. Seder ◽  
Wibisono Hartojo ◽  
Lin Lin ◽  
Amy L. Silvers ◽  
Zhuwen Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Poor Survival ◽  
Promote Cell Proliferation

DBX2 promotes glioblastoma cell proliferation by regulating REST expression

2021 ◽  
Vol 22 ◽  
Author(s):  
Ruixing He ◽  
Xiaotian Zhang ◽  
Lianshu Ding
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Brain Cancer ◽  
Binding Sites ◽  
Promoter Region ◽  
Poor Prognosis ◽  
Positive Relationship ◽  
Colony Formation Assay ◽  
Loss Of Function ◽  
Promote Cell Proliferation

Background: Glioblastoma (GBM) is the most common but lethal brain cancer with poor prognosis. The developing brain homeobox 2 (DBX2) has been reported to play important roles in tumor growth. However, the mechanisms of DBX2 in GBM are still unknown. Objective: This study aims to investigate the function and mechanisms of DBX2 in GBM. Methods: The expressions of DBX2 and REST in GBM were measured by analyzing data from databases, and the results were checked by qPCR and/or western blot of GBM cell lines. Cell proliferation was determined by CCK8 assay, immunohistochemistry and colony formation assay. ChIP-qPCR was used to determine the binding sites of DBX2 on REST. Results: In this study, we found that the expression of DBX2 was upregulated in the GBM cell lines. The cell proliferation was damaged after blocking DBX2 expression in U87 and U251 GBM cell lines. The expression level of DBX2 had a positive relationship with that of REST. Our ChIP-qPCR results showed that DBX2 is directly bound to the promoter region of REST. Additionally, the increased GBM cell proliferation caused by DBX2 overexpression can be rescued by REST loss of function. Conclusion: DBX2 could promote cell proliferation of GBM by binding to the promoter region of REST gene and increasing REST expression.

scholarly journals Linc00152 promotes Cancer Cell Proliferation and Invasion and Predicts Poor Prognosis in Lung adenocarcinoma

2017 ◽  
Vol 8 (11) ◽  
pp. 2042-2050 ◽  
Author(s):  
Pei-pei Zhang ◽  
Yi-qin Wang ◽  
Wei-wei Weng ◽  
Wei Nie ◽  
Yong Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Cancer Cell ◽  
Poor Prognosis ◽  
Cancer Cell Proliferation ◽  
Proliferation And Invasion

scholarly journals Increased extracellular signal regulated kinases phosphorylation in the adrenal gland in response to chronic ACTH treatment

2007 ◽  
Vol 192 (3) ◽  
pp. 647-658 ◽  
Author(s):  
Jorge G Ferreira ◽  
Célia D Cruz ◽  
Delminda Neves ◽  
Duarte Pignatelli
Keyword(s):  
Cell Proliferation ◽  
Mek Inhibitor ◽  
Nuclear Antigen ◽  
Dependent Manner ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Extracellular Stimuli ◽  
Corticosterone Release

ACTH released from the pituitary acts through activation of cAMP/PKA in adrenocortical cells stimulating steroidogenesis. Although ACTH was originally thought to have anti-proliferative effects on the adrenal, recently it has been described that it could also have proliferative effects acting through other signalling cascades. This is also relevant in humans given the increased levels of ACTH occurring together with adrenal cortex hyperplasia observed in Cushing’s disease and possibly in other situations such as chronic stress. One of the signalling pathways regulating cell proliferation is the extracellular signal regulated kinase (ERKs) pathway. ERKs are members of the MAPK family of cascades. They are activated by extracellular stimuli such as growth factors and mitogens, become phosphorylated through MEK1/2 and regulate a diversity of cellular processes such as proliferation and differentiation. Until now, no study addressed the effects of chronic ACTH administration on the activation of ERKs in vivo. Using rats submitted to different ACTH dosages as well as variable durations, we determined if ACTH induced ERKs activation and by establishing a parallelism with proliferating cell nuclear antigen (PCNA) expression, we aimed to demonstrate a role of ACTH-induced ERKs activation in cell proliferation. Blood was collected for hormonal analysis and the role of ACTH-induced ERKs activation in the stimulation of steroidogenesis was also studied. We confirmed that ACTH increased adrenal weight and corticosterone levels when compared with control or dexamethasone-treated animals. We also demonstrated that ACTH increases ERKs activation and PCNA expression in a time- and dose-dependent manner. When ERKs activation was blocked by the use of a specific MEK inhibitor (PD98059), there was a decrease in ACTH-induced corticosterone release and PCNA expression. We conclude that chronic ACTH induces ERKs activation and that this plays an important role in the induction of cell proliferation as well as steroidogenesis.

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