scholarly journals Aldolase A Promotes Proliferation and Metastasis of Colorectal Cancer through Targeting COPS6 and Regulating MAPK Signaling Pathway

2021 ◽  
Author(s):  
Ya Lu ◽  
Yuan Zhang ◽  
Hui Zhang ◽  
Yue Zhu ◽  
Junying Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Invasion And Migration ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Aldolase A

Abstract Background: Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms needs further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the function and mechanism of ALDOA in CRC remain unclear. We aimed to evaluate the biological role of ALDOA in CRC.Methods: The stable ALDOA knockdown or overexpression cell lines were established for subsequent experiments. The qRT-PCR and western blotting were used to detect the expression of ALDOA and COPS6 and the relative protein levels of epithelial-mesenchymal transition (EMT) and MAPK signaling pathway. Immunofluorescence (IF) assay was applied to determine ALDOA localization. CCK-8, transwell, and wound healing assays were performed to evaluate CRC cell proliferation, invasion, and migration. Mouse xenograft models were established to verify the effect of ALDOA on CRC cell growth in vivo. Immunoprecipitation (IP) assay and mass spectrometry (MS) analysis were conducted to identify the interactions between ALDOA and COPS6.Results: ALDOA was overexpressed in CRC tissues and cell lines. Silencing ALDOA significantly impaired the proliferation, invasion and migration of CRC cells in vitro, and obviously decreased the growth of CRC cells in vivo. Mechanically, ALDOA bound to and regulated COPS6, and the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by the depletion of COPS6. Besides, EMT program and MAPK signaling pathway were activated by ALDOA overexpression.Conclusion: ALDOA facilitated the proliferation, invasion and migration of CRC through binding and regulating COPS6, inducing EMT and activating MAPK signaling pathway.

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

scholarly journals TIMP-2 Regulates 5-Fu Resistance via the ERK/MAPK Signaling Pathway in Colorectal Cancer

2020 ◽  
Author(s):  
Guolin Zhang ◽  
Xin Luo ◽  
Jianbin Xu ◽  
Wei Zhang ◽  
Engeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Resistance Mechanism ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Erk Mapk ◽  
Colorectal Cancer Patients ◽  
Autocrine Mechanism

Abstract Background: 5-Fluorouracil (5-Fu) is the first-line chemotherapeutic drug in the treatment of colorectal cancer. The efficiency of 5-Fu is limited by drug resistance in colorectal cancer patients. This study was aimed to define the functions of tissue inhibitor metalloproteinases 2 (TIMP-2) in the 5-Fu resistance to colorectal cancer and investigate its potential mechanism.Methods: Cytokine array, ELISA and RT-qPCR were performed to detect cytokine expression levels. Western blot and immunohistochemistry were used to show the differential expression of proteins. In addition, cell viability was detected by CCK-8.Results: We established that there is an up-regulation in the expression of the TIMP-2 in colorectal cancer patients. This up-regulation in TIMP-2 expression was evident in 5-Fu resistant colorectal cancer patients and resulted in a poor prognosis. Besides, in vivo, clinical studies and patient-derived xenograft (PDX) models confirmed that TIMP-2 was highly expressed in the 5-Fu-resistant colorectal cancer. We deduced an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway via an autocrine mechanism. The 5-Fu resistance could overcome by the inhibition of TIMP-2 by anti-TIMP-2 antibody or ERK/MAPK by U0126.Conclusion: Our findings identify a TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism in colorectal cancer. Moreover, we recommend the use of an ERK/MAPK signal pathway inhibitor or TIMP-2-mediated immunotherapy for 5-Fu resistant colorectal cancer.

Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway

2012 ◽  
Vol 26 (3) ◽  
pp. 381-392 ◽  
Author(s):  
Hua Liang ◽  
Miaoning Gu ◽  
Chengxiang Yang ◽  
Hanbing Wang ◽  
Xianjie Wen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

Bone Marrow Mesenchymal Stem Cells (BMSC)-Derived MicroRNA-189 Inhibits Glioma Tumorigenesis Through Suppressing Tumor Necrosis Factor-α (TNF-α)-Mediated Nuclear Factor Kappa Light Chain Enhancer of Activated B Cells (NF-κB) Signaling Pathway

2022 ◽  
Vol 12 (3) ◽  
pp. 581-587
Author(s):  
Wenxu Rao ◽  
Kang Yin
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Inflammatory Factors ◽  
Invasion And Migration ◽  
Marrow Mesenchymal Stem Cells ◽  
And Migration

This study aims at investigating the mechanism underlying bone marrow mesenchymal stem cells (BMSC) function in glioma. Glioma cells were administered with plasmids loading NF-κB siRNA, microRNA (miRNA)-189 inhibitor, or miR-189 mimics for transfection followed by analysis of miR-189 expression by RT-qPCR, cell apoptosis by flow cytometry, cell proliferation by MTT assay,invasion and migration by Transwell assay, inflammatory factors secretion by ELISA as well as proteins expression by western blot. A mouse model of glioma was established to detect the in vivo effect of BMSCs. miR-189 was lowly expressed in glioma cell lines but enriched in BMSCs. When miR-189 was silenced, cell proliferation, invasion and migration were potentiated and apoptosis was decreased, along with enhancement of N-cadherin, Vimentin, MMP-2 and and MMP-9, and decline in Bax, cleaved casepase-3 and cleaved PARP. Silencing of NF-κB reversed the effect of miR-189 inhibitor on cell progression, accompanied with reduction of inflammatory factors. BMSCs treatment effectively promoted miR-189 expression in glioma and inactivated TNF-α/NF-κB signaling, thereby suppressing tumor growth. In conclusion, miR-189 derived from BMSC inhibits glioma progression through regulation of TNF-α/NF-κB signaling pathway.

scholarly journals Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

2017 ◽  
Vol 41 (5) ◽  
pp. 1851-1864 ◽  
Author(s):  
Ren-hong Huang ◽  
Ying-jun Quan ◽  
Jin-hong Chen ◽  
Ting-feng Wang ◽  
Ming Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Hct116 Cell ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cell Counting ◽  
Migration And Invasion

Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. Methods: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.

A VEGFR2 Antagonist Inhibits Cell Proliferation, Migration, and Invasion by Blocking the PI3K-Akt and MAPK Signaling Pathways in Thyroid Cancer

2021 ◽  
Author(s):  
Chunhao Liu ◽  
Zhao Liu ◽  
Hao Zhao ◽  
Yue Cao ◽  
Yansong Lin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cell Lines ◽  
Mapk Signaling ◽  
Vascular Endothelial ◽  
Antitumor Effects ◽  
Invasion And Migration ◽  
And Migration ◽  
Mapk Signaling Pathways

Abstract Background: Vascular endothelial growth factor receptor-2 (VEGFR2)-mediated signaling cascades are involved in proliferation, migration, survival, and permeability changes in vascular endothelial cells. It was thought that VEGFR2 antagonists exerted their antitumor effects by inhibiting angiogenesis in tumor tissues. However, some recent studies have found that they have significant direct antitumor effects in some tumors. The aim of this study was to explore the antitumor effects and mechanisms of VEGFR2 antagonists in thyroid cancer (TC).Methods: The antitumor efficacy of a VEGFR2 antagonist (apatinib) in TC cells was evaluated through a series of in vitro experiments, and xenograft models were used to test its in vivo antitumor activity. The antitumor mechanisms of the VEGFR2 antagonist were explored using western blotting and immunohistochemistry.Results: Compared with that in the normal human thyroid cell line HTori3, the expression of VEGFR2 in TC cell lines (including IHH4, BCPAP, TPC-1, C643, K1, and 8305C) was significantly increased, especially in the C643 and 8305C cell lines. VEGFR2 antagonist inhibited the proliferation of C643 and 8305C cells in a dose-dependent manner, significantly reduced the invasion and migration of these cells, induced G0/G1 phase arrest and promoted cancer cell apoptosis. Additionally, the antiproliferative effect of the VEGFR2 antagonist was significantly reduced after KDR gene knockdown. In vivo experiments showed that tumor growth in nude mice was significantly inhibited in response to apatinib. The western blot and immunohistochemistry results showed that the VEGFR2 antagonist significantly reduced the expression and phosphorylation of VEGFR2 and further inhibited the phosphorylation of the downstream molecules Akt and ERK1/2.Conclusions: The VEGFR2 antagonist inhibited cell proliferation, invasion and migration in TC by inhibiting the PI3K/Akt and MAPK signaling pathways and exerted direct antitumor effects. Thus, directly targeting VEGFR2 can be an effective strategy for TC expressing VEGFR2.

scholarly journals Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation

2017 ◽  
Vol 42 (2) ◽  
pp. 729-742 ◽  
Author(s):  
Caihua Wang ◽  
Peiwei Li ◽  
Junmei Xuan ◽  
Chunpeng Zhu ◽  
Jingjing Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Ldl Receptor ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
High Fat

Background/Aims: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. Methods: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. Results: The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR) expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of “stemness” genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD) significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS) levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK) signaling pathway. Conclusions: LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored.

scholarly journals The interplay among MAP3K1 and SOX2 regulated metastasis by MAPK signaling pathway through interaction with KLF4 in triple-negative breast cancer

2021 ◽  
Author(s):  
Lixiang Zheng ◽  
Xilei Zheng ◽  
Xiaoying Ren ◽  
Ping Hunag ◽  
Ke Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Expression Level ◽  
Cause Of Deaths ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Abstract BackgroundTumor metastasis with poor prognosis is still the leading cause of deaths among triple-negative breast caner (TNBC) patients. Therefore, understanding the underlying molecular mechanisms of TNBC metastasis and identifying the molecules contributing to the process are of great importance.It would be provided targets for the prevention and treatment of recurrence and metastasis of TNBC. MethodsThe expression level of MAP3K1 and its up-or downstream genes,SOX2 and KLF4 were detected using Western blotting assay. Cell migration and proliferation were measure by xCELLigence Real-Time Cell Analyzer (RTCA). Protein interaction was used for co-immunorecipitation. ResultCompared with metastasis (Met) in TBNC model, the expression of MAP3K1,KLF4,ERK1/2, C-jun and werelower, while SOX2, Ras,Rafand c-Fos were higher in non-metastasis (non-Met) samples. In MAP3K1 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were increased. The expression level of KLF4 was lower than SOX2 reduced or minimal interaction of both. In SOX2 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were decreased, while the expression of KLF4 and MAP3K1 were higher, the interaction of MAP3K1 and KLF4 was inhibited. ConclusionsIt is demonstrated for the very first time that SOX2 and MAP3K1 are playing an important rolesin TNBC cell metastasis by regulating MAPK signaling pathway by interacting with KLF4 .

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