scholarly journals BCKDK Promotes Epithelial Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway

2021 ◽  
Author(s):  
Huashun Li ◽  
Dongyang Yu ◽  
Lianbing Li ◽  
Juanjuan Xiao ◽  
Yijian Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Cell Transformation ◽  
Gynecologic Cancer ◽  
Erk Signaling ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Ovarian cancer is the most fatal gynecologic cancer, and epithelial ovarian cancer (EOC) is the most common type. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in many serious human diseases, including cancers. Its function in promoting cell proliferation and migration has been reported in various cancers. However, the biological role of BCKDK and its molecular mechanisms underlying EOC initiation and progression are unclear.Methods: First, the expression level of BCKDK in EOC cell lines or tissues was determined using tissue microarray (TMA)-based immunohistochemistry or western blotting. Then, growth curve analysis, anchorage-independent cell transformation assays, wound healing assays, cell migration assays, and tumor xenografts were used to test whether BCKDK could promote cell transformation or metastasis. Finally, the signaling pathways involved in this process were investigated by western blotting or immunoprecipitation.Results: We found that the expression of BCKDK was upregulated in EOC tissues and that high expression of BCKDK was correlated with an advanced pathological grade in patients. The ectopic overexpression of BCKDK promoted the proliferation and migration of EOC cells, and the knockdown of BCKDK with shRNAs inhibited the proliferation and migration of EOC ex vivo and in vivo. Moreover, BCKDK promoted EOC proliferation and migration by activating MEK.Conclusions: Our results demonstrate that BCKDK promotes EOC proliferation and migration by activating the MEK/ERK signaling pathway. Targeting the BCKDK-MEK axis may provide a new therapeutic strategy for treating patients with EOC.

scholarly journals BCKDK Promotes EOC Proliferation and Migration By Activating The MEK/ERK Signaling Pathway

2021 ◽  
Author(s):  
Huashun Li ◽  
Dongyang Yu ◽  
Lianbing Li ◽  
Juanjuan Xiao ◽  
Yijian Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Cell Transformation ◽  
Ex Vivo ◽  
Gynecologic Cancer ◽  
Erk Signaling ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Ovarian cancer is the most fatal gynecologic cancer, and epithelial ovarian cancer (EOC) is the most common type. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in many serious human diseases, including cancers. Its function in promoting cell proliferation and migration has been reported in various cancers. However, the biological role of BCKDK and its molecular mechanisms underlying EOC initiation and progression are unclear.Methods: First, the expression level of BCKDK in EOC cell lines or tissues was determined using tissue microarray (TMA)-based immunohistochemistry or western blotting. Then, growth curve analysis, anchorage-independent cell transformation assays, wound healing assays, cell migration assays, and tumor xenografts were used to test whether BCKDK could promote cell transformation or metastasis. Finally, the signaling pathways involved in this process were investigated by western blotting or immunoprecipitation.Results: We found that the expression of BCKDK was upregulated in EOC tissues and that high expression of BCKDK was correlated with an advanced pathological grade in patients. The ectopic overexpression of BCKDK promoted the proliferation and migration of EOC cells, and the knockdown of BCKDK with shRNAs inhibited the proliferation and migration of EOC ex vivo and in vivo. Moreover, BCKDK promoted EOC proliferation and migration by targeting MEK.Conclusions: Our results demonstrate that BCKDK promotes EOC proliferation and migration by activating the MEK/ERK signaling pathway. Targeting the BCKDK-MEK axis may provide a new therapeutic strategy for treating patients with EOC.

scholarly journals TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

2021 ◽  
Vol 10 ◽  
Author(s):  
Mengya Zhong ◽  
Xingfeng Qiu ◽  
Yu Liu ◽  
Yan Yang ◽  
Lei Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hct116 Cells ◽  
Proliferation And Migration

Tumor necrosis factor-induced protein-8 (TIPE) is highly expressed in colorectal cancer (CRC). Decoy receptor 3 (DcR3) is a soluble secreted protein that can antagonize Fas ligand (FasL)-induced apoptosis and promote tumorigenesis. It remains unclear whether TIPE can regulate DcR3 expression. In this study, we examined this question by analyzing the relationship between these factors in CRC. Bioinformatics and tissue microarrays were used to determine the expression of TIPE and DcR3 and their correlation in CRC. The expression of TIPE and DcR3 in colon cancer cells was detected. Plasma samples were collected from CRC patients, and DcR3 secretion was measured. Then, dual-luciferase reporter gene analysis was performed to assess the interaction between TIPE and DcR3. We exogenously altered TIPE expression and analyzed its function and influence on DcR3 secretion. Lipopolysaccharide (LPS) was used to stimulate TIPE-overexpressing HCT116 cells, and alterations in signaling pathways were detected. Additionally, inhibitors were used to confirm molecular mechanisms. We found that TIPE and DcR3 were highly expressed in CRC patients and that their expression levels were positively correlated. DcR3 was highly expressed in the plasma of cancer patients. We confirmed that TIPE and DcR3 were highly expressed in HCT116 cells. TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter. TIPE activated the PI3K/AKT signaling pathway to regulate the expression of DcR3, thereby promoting cell proliferation and migration and inhibiting apoptosis. In summary, TIPE and DcR3 are highly expressed in CRC, and both proteins are associated with poor prognosis. TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC, thus promoting cell proliferation and migration and inhibiting apoptosis. These findings may have clinical significance and promise for applications in the treatment or prognostication of CRC.

scholarly journals Actin Beta-Like 2 as a New Mediator of Proliferation and Migration in Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Nicole Elisabeth Topalov ◽  
Doris Mayr ◽  
Clemens Scherer ◽  
Anca Chelariu-Raicu ◽  
Susanne Beyer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Regulatory Element ◽  
Prognostic Impact ◽  
Activated T Cells ◽  
And Migration ◽  
Sirna Knockdown ◽  
The Impact ◽  
Proliferation And Migration

The impact of Actin beta-like 2 (ACTBL2), a novel described actin isoform, on epithelial ovarian cancer (EOC) biology has not been investigated so far. In this study, we analyzed the prognostic and functional significance of ACTBL2 and its regulatory element Nuclear factor of activated T-cells 5 (NFAT5). The expression of ACTBL2 and NFAT5 was examined in tissue microarrays of 156 ovarian cancer patients by immunohistochemistry. Aiming to assess the molecular impact of ACTBL2 on cellular characteristics, functional assays were executed in vitro upon siRNA knockdown of ACTBL2 and NFAT5. ACTBL2 expression was identified as an independent negative prognostic factor for overall survival of EOC patients. EOC cell lines showed a significantly increased mRNA and protein level of ACTBL2 compared to the benign control. In vitro analyses upon siRNA knockdown of ACTBL2 displayed a significantly reduced cellular viability, proliferation and migration. siRNA knockdown of NFAT5 proved a significant molecular interplay by inducing a downregulation of ACTBL2 with a thus resulting concordant alteration in cellular functions, predominantly reflected in a decreased migratory potential of EOC cells. Our results provide significant evidence on the negative prognostic impact of ACTBL2 in EOC, suggesting its crucial importance in ovarian carcinogenesis by modulating cellular motility and proliferation.

scholarly journals FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance by stabilizing ELAVL1 protein and regulating downstream Rab10/TLR4 pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanhui Li ◽  
Yue Xiong ◽  
Zhen Wang ◽  
Jianjun Han ◽  
Sufang Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Histological Grade ◽  
Mechanistic Studies ◽  
Gene Interaction Network ◽  
Kaplan Meier ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Breast cancer (BC) is one of the most common cancers and the leading cause of death in women. Previous studies have demonstrated that FAM49B is implicated in several tumor progression, however, the role and mechanism of FAM49B in BC remain to be explored. Therefore, in this study, we aimed to systematically study the role of FAM49B in the proliferation, metastasis, apoptosis, and chemoresistance of BC, as well as the corresponding molecular mechanisms and downstream target. Methods The ONCOMINE databases and Kaplan–Meier plotter databases were analyzed to find FAM49B and its prognostic values in BC. FAM49B expression in BC and adjacent non-tumor tissues was detected by western blot and IHC. Kaplan–Meier analysis was used to identify the prognosis of BC patients. After FAM49B knockdown in MCF-7 and MDA-MB-231 cells, a combination of co-immunoprecipitation, MTT, migration, and apoptosis assays, nude mouse xenograft tumor model, in addition to microarray detection and data analysis was used for further mechanistic studies. Results In BC, the results showed that the expression level of FAM49B was significantly higher than that in normal breast tissue, and highly expression of FAM49B was significantly positively correlated with tumor volume, histological grade, lymph node metastasis rate, and poor prognosis. Knockdown of FAM49B inhibited the proliferation and migration of BC cells in vitro and in vivo. Microarray analysis revealed that the Toll-like receptor signaling pathway was inhibited upon FAM49B knockdown. In addition, the gene interaction network and downstream protein validation of FAM49B revealed that FAM49B positively regulates BC cell proliferation and migration by promoting the Rab10/TLR4 pathway. Furthermore, endogenous FAM49B interacted with ELAVL1 and positively regulated Rab10 and TLR4 expression by stabilizing ELAVL1. Moreover, mechanistic studies indicated that the lack of FAM49B expression in BC cells conferred more sensitivity to anthracycline and increased cell apoptosis by downregulating the ELAVL1/Rab10/TLR4/NF-κB signaling pathway. Conclusion These results demonstrate that FAM49B functions as an oncogene in BC progression, and may provide a promising target for clinical diagnosis and therapy of BC.

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