Role of p38 MAPK pathway in BMP4-mediated Smad-dependent premature senescence in lung cancer cells

BMP4 (bone morphogenetic protein 4) is a multifunctional cytokine known to exert its biological effects through a variety of signalling pathways. The diverse function of BMP4 appears to be due to multiple pathways activated by BMP4 itself. Our previous studies have demonstrated that BMP4 is able to drive lung cancer cells into a process of premature senescence; however, the signalling pathways, as well their interplays and roles associated with this process, are not well understood. To address these questions, in the present study we investigated the signalling and molecular mechanisms underlying the BMP4-induced senescence, and our data demonstrated that p38 MAPK (mitogen-activated protein kinase) and Smad pathways were necessary for this process. Meanwhile, the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which is required for senescence, was not activated by BMP4 in the lung cancer cell line NCI-H460. We also showed that the BMP4-responsive R-Smads (receptor-regulated Smads), i.e. Smad1 and Smad5, were necessary for the up-regulation of p16INK4a and p21WAF1/cip1 and for the induction of premature senescence. Furthermore, we found that activation of the p38 MAPK pathway by BMP4 was essential for the full activation of transcription potential of Smad1/5. Overall, the results of the present study implicate a complex co-operation between p38 MAPK and Smad pathways in BMP4-mediated premature senescence.

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Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK pathway and GADD153

Neoplasma ◽

10.4149/neo_2011_06_482 ◽

2011 ◽

Vol 58 (6) ◽

pp. 482-490 ◽

Cited By ~ 58

Author(s):

N. WU ◽

C. GU ◽

H. GU ◽

H. HU ◽

Y. HAN ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

P38 Mapk ◽

Mapk Pathway ◽

Lung Cancer Cells ◽

P38 Mapk Pathway

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Quercetin induces cell death by caspase-dependent and p38 MAPK pathway in EGFR mutant lung cancer cells

Kosin Medical Journal ◽

10.7180/kmj.2016.31.1.30 ◽

2016 ◽

Vol 31 (1) ◽

pp. 30

Author(s):

Eun Jin Lim ◽

Jeunghoon Heo ◽

Young-Ho Kim

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Cancer Cells ◽

P38 Mapk ◽

Mapk Pathway ◽

Lung Cancer Cells ◽

P38 Mapk Pathway ◽

Egfr Mutant

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A Ruthenium(II) N-Heterocyclic Carbene (NHC) Complex with Naphthalimide Ligand Triggers Apoptosis in Colorectal Cancer Cells via Activating the ROS-p38 MAPK Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms19123964 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3964 ◽

Cited By ~ 10

Author(s):

Yasamin Dabiri ◽

Alice Schmid ◽

Jannick Theobald ◽

Biljana Blagojevic ◽

Wojciech Streciwilk ◽

...

Keyword(s):

Cancer Cells ◽

P38 Mapk ◽

Molecular Mechanisms ◽

Mapk Pathway ◽

P38 Mapk Pathway ◽

Anti Cancer ◽

Colorectal Cancer Cells ◽

Cellular Reactive Oxygen Species ◽

Cancer Types ◽

Apoptotic Effects

The p38 MAPK pathway is known to influence the anti-tumor effects of several chemotherapeutics, including that of organometallic drugs. Previous studies have demonstrated the important role of p38 both as a regulator and a sensor of cellular reactive oxygen species (ROS) levels. Investigating the anti-cancer properties of novel 1,8-naphthalimide derivatives containing Rh(I) and Ru(II) N-heterocyclic carbene (NHC) ligands, we observed a profound induction of ROS by the complexes, which is most likely generated from mitochondria (mtROS). Further analyses revealed a rapid and consistent activation of p38 signaling by the naphthalimide-NHC conjugates, with the Ru(II) analogue—termed MC6—showing the strongest effect. In view of this, genetic as well as pharmacological inhibition of p38α, attenuated the anti-proliferative and pro-apoptotic effects of MC6 in HCT116 colon cancer cells, highlighting the involvement of this signaling molecule in the compound’s toxicity. Furthermore, the influence of MC6 on p38 signaling appeared to be dependent on ROS levels as treatment with general- and mitochondria-targeted anti-oxidants abrogated p38 activation in response to MC6 as well as the molecule’s cytotoxic- and apoptogenic response in HCT116 cells. Altogether, our results provide new insight into the molecular mechanisms of naphthalimide-metal NHC analogues via the ROS-induced activation of p38 MAPK, which may have therapeutic interest for the treatment of various cancer types.

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Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

Cancer Biomarkers ◽

10.3233/cbm-210189 ◽

2021 ◽

pp. 1-9

Author(s):

Huan Guo ◽

Baozhen Zeng ◽

Liqiong Wang ◽

Chunlei Ge ◽

Xianglin Zuo ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Lung Cancer Cells ◽

Invasion And Migration ◽

And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

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PRMT5 Promotes EMT Through Regulating Akt Activity in Human Lung Cancer

Cell Transplantation ◽

10.1177/09636897211001772 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110017

Author(s):

Jianhao Huang ◽

Yonghua Zheng ◽

Xiao Zheng ◽

Bao Qian ◽

Qi Yin ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Human Lung ◽

Akt Signaling ◽

Lung Cancer Cells ◽

Signaling Cascades ◽

Human Lung Cancer ◽

Mesenchymal Transition ◽

Human Lung Cancer Cells

The type II protein arginine methyltransferase 5 (PRMT5) has been engaged in various human cancer development and progression types. Nevertheless, few studies uncover the biological functions of PRMT5 in the epithelial-mesenchymal transition (EMT) of human lung cancer cells, and the associated molecular mechanisms and signaling cascades are entirely unknown. Here, we show that PRMT5 is the ectopic expression in human lung cancer tissues and cell lines. Further study reveals that silencing PRMT5 by lentivirus-mediated shRNA or blocking of PRMT5 by specific inhibitor GSK591 attenuates the expression levels of EMT-related markers in vivo, using the xenograft mouse model. Moreover, our results show that down-regulation of PRMT5 impairs EGFR/Akt signaling cascades in human lung cancer cells, whereas re-expression of PRMT5 recovers those changes, suggesting that PRMT5 regulates EMT probably through EGFR/Akt signaling axis. Altogether, our results demonstrate that PRMT5 serves as a critical oncogenic regulator and promotes EMT in human lung cancer cells. More importantly, our findings also suggest that PRMT5 may be a potential therapeutic candidate for the treatment of human lung cancer.

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MicroRNA-7–regulated TLR9 signaling–enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway

Molecular Biology of the Cell ◽

10.1091/mbc.e12-07-0519 ◽

2013 ◽

Vol 24 (1) ◽

pp. 42-55 ◽

Cited By ~ 52

Author(s):

Lin Xu ◽

Zhenke Wen ◽

Ya Zhou ◽

Zhongmin Liu ◽

Qinchuan Li ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Biological Effects ◽

Tumor Biology ◽

Metastatic Potential ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Tlr9 Signaling

Recent evidence shows that microRNAs (miRNAs) contribute to the biological effects of Toll-like receptor (TLR) signaling on various cells. Our previous data showed that TLR9 signaling could enhance the growth and metastatic potential of human lung cancer cells. However, the potential role of miRNAs in the effects of TLR9 signaling on tumor biology remains unknown. In this paper, we first report that TLR9 signaling could reduce intrinsic miR-7 expression in human lung cancer cells. Furthermore, overexpression of miR-7 can significantly inhibit TLR9 signaling–enhanced growth and metastatic potential of lung cancer cells in vitro and in vivo. Notably, we identify phosphoinositide-3-kinase, regulatory subunit 3 (PIK3R3) as a novel target molecule of miR-7 in lung cancer cells by Western blotting and luciferase report assay. Further study shows that miR-7 inhibits the effects of TLR9 signaling on lung cancer cells through regulation of the PIK3R3/Akt pathway. These data suggest that miR-7 could act as a fine-tuner in regulating the biological effects of TLR9 signaling on human lung cancer cells, which might be helpful to the understanding of the potential role of miRNAs in TLR signaling effects on tumor biology.

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