BAG2 Promotes Proliferation and Metastasis of Gastric Cancer via ERK1/2 Signaling and Partially Regulated by miR186

Sun, Lisha; Chen, Guanglei; Sun, An-Qi; Wang, Zheng; Huang, Haibo; Gao, Zhiqiang; Liang, W M; Liu, Caigang; Li, Kai

doi:10.3389/fonc.2020.00031

Cited by 26 publications

(37 citation statements)

References 41 publications

(35 reference statements)

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“…Among its targets, one of the most important is the heat shock protein 70 (Hsp70) [ 36 ]. In agreement with our study, BAG2 is frequently found to be upregulated in tumors, pointing out its ability to also promote proliferation and metastasis by promoting the accumulation of mutant p53 [ 37 , 38 , 39 , 40 ]. According to the results of our work and the knowledge on BAG2, studies evaluating strategies targeting BAG2 in the fight against MPM should be undertaken.…”

Section: Discussionsupporting

confidence: 92%

Identification of Overexpressed Genes in Malignant Pleural Mesothelioma

Morani

Bisceglia

Rosini

et al. 2021

IJMS

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Malignant pleural mesothelioma (MPM) is a fatal tumor lacking effective therapies. The characterization of overexpressed genes could constitute a strategy for identifying drivers of tumor progression as targets for novel therapies. Thus, we performed an integrated gene-expression analysis on RNAseq data of 85 MPM patients from TCGA dataset and reference samples from the GEO. The gene list was further refined by using published studies, a functional enrichment analysis, and the correlation between expression and patients’ overall survival. Three molecular signatures defined by 15 genes were detected. Seven genes were involved in cell adhesion and extracellular matrix organization, with the others in control of the mitotic cell division or apoptosis inhibition. Using Western blot analyses, we found that ADAMTS1, PODXL, CIT, KIF23, MAD2L1, TNNT1, and TRAF2 were overexpressed in a limited number of cell lines. On the other hand, interestingly, CTHRC1, E-selectin, SPARC, UHRF1, PRSS23, BAG2, and MDK were abundantly expressed in over 50% of the six MPM cell lines analyzed. Thus, these proteins are candidates as drivers for sustaining the tumorigenic process. More studies with small-molecule inhibitors or silencing RNAs are fully justified and need to be undertaken to better evaluate the cancer-driving role of the targets herewith identified.

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Section: Discussionsupporting

confidence: 92%

Identification of Overexpressed Genes in Malignant Pleural Mesothelioma

Morani

Bisceglia

Rosini

et al. 2021

IJMS

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“…BAG2 signaling was predicted to be active after AUY-VE, although its protein level was decreased, according to the proteome analysis. BAG2 interacts with HSP70 to regulate its functions and suppresses apoptosis induction via BCL2 protein interactions [ 61 , 62 ]. Thus, reduced BAG2 and high HSP70 levels might contribute to CMA and apoptosis induction in A673 cells.…”

Section: Discussionmentioning

confidence: 99%

Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing’s sarcoma cells

et al. 2021

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Introduction Ewing's sarcoma is an aggressive childhood malignancy whose outcome has not substantially improved over the last two decades. In this study, combination treatments of the HSP90 inhibitor AUY922 with either the ATR inhibitor VE821 or the ATM inhibitor KU55933 were investigated for their effectiveness in Ewing's sarcoma cells. Methods Effects were determined in p53 wild-type and p53 null Ewing's sarcoma cell lines by flow cytometric analyses of cell death, mitochondrial depolarization and cell-cycle distribution as well as fluorescence and transmission electron microscopy. They were molecularly characterized by gene and protein expression profiling, and by quantitative whole proteome analysis. Results AUY922 alone induced DNA damage, apoptosis and ER stress, while reducing the abundance of DNA repair proteins. The combination of AUY922 with VE821 led to strong apoptosis induction independent of the cellular p53 status, yet based on different molecular mechanisms. p53 wild-type cells activated pro-apoptotic gene transcription and underwent mitochondria-mediated apoptosis, while p53 null cells accumulated higher levels of DNA damage, ER stress and autophagy, eventually leading to apoptosis. Impaired PI3K/AKT/mTOR signaling further contributed to the antineoplastic combination effects of AUY922 and VE821. In contrast, the combination of AUY922 with KU55933 did not produce a cooperative effect. Conclusion Our study reveals that HSP90 and ATR inhibitor combination treatment may be an effective therapeutic approach for Ewing's sarcoma irrespective of the p53 status.

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“…Interestingly, IGF2BP3 has been found to be associated with chemotherapy resistance and poor prognosis of ovarian cancer (31)(32)(33). BAG2 can promote the metastasis and proliferation of gastric cancer (34). By affecting the MAPK/JNK signal pathway (35), RNF213 can inhibit the carcinogenesis of glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

Systematic Profiling of Alternative Splicing Events in Ovarian Cancer

Liu

Wang

et al. 2021

Front. Oncol.

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Alternative splicing (AS) is significantly related to the development of tumor and the clinical outcome of patients. In this study, our aim was to systematically analyze the survival-related AS signal in ovarian serous cystadenocarcinoma (OV) and estimate its prognostic validity in 48,049 AS events out of 21,854 genes. We studied 1,429 AS events out of 1,125 genes, which were significantly related to the overall survival (OS) in patients with OV. We established alternative splicing features on the basis of seven AS events and constructed a new comprehensive prognostic model. Kaplan-Meier curve analysis showed that seven AS characteristics and comprehensive prognostic models could strongly stratify patients with ovarian cancer and make them distinctive prognosis. ROC analysis from 0.781 to 0.888 showed that these models were highly efficient in distinguishing patient survival. We also verified the prognostic characteristics of these models in a testing cohort. In addition, uni-variate and multivariate Cox analysis showed that these models were superior independent risk factors for OS in patients with OV. Interestingly, AS events and splicing factor (SFs) networks revealed an important link between these prognostic alternative splicing genes and splicing factors. We also found that the comprehensive prognosis model signature had higher prediction ability than the mRNA signature. In summary, our study provided a possible prognostic prediction model for patients with OV and revealed the splicing network between AS and SFs, which could be used as a potential predictor and therapeutic target for patients with OV.

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BAG2 Promotes Proliferation and Metastasis of Gastric Cancer via ERK1/2 Signaling and Partially Regulated by miR186

Cited by 26 publications

References 41 publications

Identification of Overexpressed Genes in Malignant Pleural Mesothelioma

Identification of Overexpressed Genes in Malignant Pleural Mesothelioma

Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing’s sarcoma cells

Systematic Profiling of Alternative Splicing Events in Ovarian Cancer

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