Placenta-specific 8 (PLAC8) mediates inflammation and mobility of the hPDLCs via MEK/ERK signaling pathway

AbstractFucosterol, a sterol isolated from brown algae, has been demonstrated to have anti-cancer properties. However, the effects and underlying molecular mechanism of fucosterol on non-small cell lung cancer remain to be elucidated. In this study, the corresponding targets of fucosterol were obtained from PharmMapper, and NSCLC related targets were gathered from the GeneCards database, and the candidate targets of fucosterol-treated NSCLC were predicted. The mechanism of fucosterol against NSCLC was identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein–protein interaction data were collected from STRING database. The hub gene GRB2 was further screened out and verified by molecular docking. Moreover, the relationship of GRB2 expression and immune infiltrates were analyzed by the TIMER database. The results of network pharmacology suggest that fucosterol acts against candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8, and SRC, which regulate biological processes including negative regulation of the apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf/MEK/ERK signaling pathway initiated by GRB2 showed to be significant in treating NSCLC. In conclusion, our study indicates that fucosterol may suppress NSCLC progression by targeting GRB2 activated the Raf/MEK/ERK signaling pathway, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

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Anti-angiogenesis Function of Ononin via Suppressing the MEK/Erk Signaling Pathway

Journal of Natural Products ◽

10.1021/acs.jnatprod.1c00008 ◽

2021 ◽

Author(s):

Guowei Gong ◽

Yuzhong Zheng ◽

Xiangpeng Kong ◽

Zhen Wen

Keyword(s):

Signaling Pathway ◽

Erk Signaling

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Reactive oxygen species rescue regeneration after silencing the MAPK–ERK signaling pathway in Schmidtea mediterranea

Scientific Reports ◽

10.1038/s41598-020-79588-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

V. Jaenen ◽

S. Fraguas ◽

K. Bijnens ◽

M. Heleven ◽

T. Artois ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Signaling Pathway ◽

Reactive Oxygen ◽

Light Therapy ◽

Erk Signaling ◽

Model Organisms ◽

Ros Production ◽

Oxygen Species ◽

Planarian Regeneration ◽

Egfr Signaling Pathway

AbstractDespite extensive research on molecular pathways controlling the process of regeneration in model organisms, little is known about the actual initiation signals necessary to induce regeneration. Recently, the activation of ERK signaling has been shown to be required to initiate regeneration in planarians. However, how ERK signaling is activated remains unknown. Reactive Oxygen Species (ROS) are well-known early signals necessary for regeneration in several models, including planarians. Still, the probable interplay between ROS and MAPK/ERK has not yet been described. Here, by interfering with major mediators (ROS, EGFR and MAPK/ERK), we were able to identify wound-induced ROS, and specifically H2O2, as upstream cues in the activation of regeneration. Our data demonstrate new relationships between regeneration-related ROS production and MAPK/ERK activation at the earliest regeneration stages, as well as the involvement of the EGFR-signaling pathway. Our results suggest that (1) ROS and/or H2O2 have the potential to rescue regeneration after MEK-inhibition, either by H2O2-treatment or light therapy, (2) ROS and/or H2O2 are required for the activation of MAPK/ERK signaling pathway, (3) the EGFR pathway can mediate ROS production and the activation of MAPK/ERK during planarian regeneration.

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Immune negative regulator TIPE2 inhibits cervical squamous cancer progression through Erk1/2 signaling

Open Life Sciences ◽

10.1515/biol-2019-0059 ◽

2019 ◽

Vol 14 (1) ◽

pp. 528-536

Author(s):

Li-Qiong Huang ◽

Bo Zheng ◽

Yi He

Keyword(s):

Cervical Cancer ◽

Western Blot ◽

Cancer Cells ◽

Signaling Pathway ◽

Erk Signaling ◽

Over Expression ◽

Squamous Cancer ◽

Cancer Tissues ◽

Proliferation And Invasion ◽

Cervical Squamous Cancer

AbstractTumor necrosis factor (TNF)-α-induced protein-8-like 2, or TIPE2, is a newly found immune negative regulatory molecule. This study further investigated the role of TIPE2 on proliferation and invasion of cervical squamous cancer cells. Expression of TIPE2 was compared in cervical squamous cancer tissues and adjacent normal tissues by Western blot and immunohistochemistry (IHC). Cervical squamous cancer cell lines, SiHa and C33A, were transfected with recombinant plasmid encoding TIPE2 and tested for cytologic characteristics. The impact of TIPE2 on phosphorylation of extracellular signal-regulated kinase (Erk) signaling pathway was also tested by Western blot analysis of key factors. TIPE2 expression was higher in cervical cancer tissues than that in normal tissue. IHC score of tumor tissue was negatively associated with lymphatic metastasis. Over expression of TIPE2 effectively inhibited the proliferation of cervical cancer cells. Wound healing and transwell assay showed that over expression of TIPE2 suppressed cell migration and invasion in vitro. Meanwhile, phosphorylation of Erk1/2 and upstream mitogen-activated protein kinase kinase (MEK) 1/2 was reduced by TIPE2. TIPE2 is negatively related with development of cervical squamous cancer. TIPE2 is an inhibitory factor of proliferation and invasion of cervical squamous cancer cells, probably through inhibiting Erk signaling pathway.

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