DUSP1 induces paclitaxel resistance through the regulation of p-glycoprotein expression in human ovarian cancer cells

Kang, Yu; Seok, Hyun Jeong; Jeong, Eun Jeong; Kim, Yuna; Yun, Seok Joong; Kim, Jung Min; Kim, Jang Seong

doi:10.1016/j.bbrc.2016.07.035

Cited by 16 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Via regulating the p38 MAPK-mediated p-glycoprotein overexpression, DUSP1 may cause the resistance of human OC cells to paclitaxel [28, 29]. The glucocorticoid administration to OC patients is correlated with increased expression of map kinase phosphatase 1 ( MKP1 , also known as DUSP1 ) and serum and glucocorticoid-regulated kinase 1 ( SGK1 ), indicating that glucocorticoids may weaken chemotherapy effect in OC patients by promoting the expression of anti-apoptotic genes [30].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis to screen the key prognostic genes in ovarian cancer

Cai

Liu

et al. 2017

J Ovarian Res

View full text Add to dashboard Cite

BackgroundOvarian cancer (OC) is a gynecological oncology that has a poor prognosis and high mortality. This study is conducted to identify the key genes implicated in the prognosis of OC by bioinformatic analysis.MethodsGene expression data (including 568 primary OC tissues, 17 recurrent OC tissues, and 8 adjacent normal tissues) and the relevant clinical information of OC patients were downloaded from The Cancer Genome Atlas database. After data preprocessing, cluster analysis was conducted using the ConsensusClusterPlus package in R. Using the limma package in R, differential analysis was performed to identify feature genes. Based on Kaplan-Meier (KM) survival analysis, prognostic seed genes were selected from the feature genes. After key prognostic genes were further screened by cluster analysis and KM survival analysis, they were performed functional enrichment analysis and multivariate survival analysis. Using the survival package in R, cox regression analysis was conducted for the microarray data of GSE17260 to validate the key prognostic genes.ResultsA total of 3668 feature genes were obtained, among which 75 genes were identified as prognostic seed genes. Then, 25 key prognostic genes were screened, including AXL, FOS, KLF6, WDR77, DUSP1, GADD45B, and SLIT3. Especially, AXL and SLIT3 were enriched in ovulation cycle. Multivariate survival analysis showed that the key prognostic genes could effectively differentiate the samples and were significantly associated with prognosis. Additionally, GSE17260 confirmed that the key prognostic genes were associated with the prognosis of OC.Conclusion AXL, FOS, KLF6, WDR77, DUSP1, GADD45B, and SLIT3 might affect the prognosis of OC.

show abstract

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis to screen the key prognostic genes in ovarian cancer

Cai

Liu

et al. 2017

J Ovarian Res

View full text Add to dashboard Cite

show abstract

“…Emerging data show that sialyltransferases also regulated chemosensitivity of cancer cells. Dualspecificity phosphatase 1 (DUSP1) activated p38 MAPK signaling to elevate expression of p-glycoprotein, which contributed to resistance of paclitaxel in ovarian cancer cells [16]. ST6Gal1 enhanced EGFR/ERK signaling to increase colon cancer proliferation and its tumor growth, decrease the cytotoxic effect of gefitinib [17].…”

Section: Introductionmentioning

confidence: 99%

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis

Wang

Zhang

Lin

et al. 2017

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3.

show abstract

“…Kim et al, found MKK3 to sustain cell motility and angiogenesis through essential molecular key players (MMP-2, MMP-9, Cdk4, Cdk2, and integrin β1) in SKOV-3 cells [18]. Kang et al, demonstrated that ectopic MKK3 drives paclitaxel resistance by inducing p-glycoprotein expression in Heya8 and Skov3ip1 cells, suggesting the involvement of MKK3-p38MAPK pathway activation in ovarian cancer drug resistance [19].…”

Section: Cervical and Ovarian Cancermentioning

confidence: 99%

Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword?

Piastra¹,

Pranteda²,

Bossi³

2022

Cancers

View full text Add to dashboard Cite

The role played by MKK3 in human cancer is controversial. MKK3 is an evolutionarily conserved protein kinase that activates in response to a variety of stimuli. Phosphorylates, specifically the p38MAPK family proteins, contribute to the regulation of a plethora of cellular processes such as proliferation, differentiation, apoptosis, invasion, and cell migration. Genes in carcinogenesis are classified as oncogenes and tumor suppressors; however, a clear distinction is not always easily made as it depends on the cell context and tissue specificity. The aim of this study is the examination of the potential contribution of MKK3 in cancer through a systematic analysis of the recent literature. The overall results reveal a complex scenario of MKK3’s involvement in cancer. The oncogenic functions of MKK3 were univocally documented in several solid tumors, such as colorectal, prostate cancer, and melanoma, while its tumor-suppressing functions were described in glioblastoma and gastric cancer. Furthermore, a dual role of MKK3 as an oncogene as well as tumor a suppressor has been described in breast, cervical, ovarian, liver, esophageal, and lung cancer. However, overall, more evidence points to its role as an oncogene in these diseases. This review indicates that the oncogenic and tumor-suppressing roles of MKK3 are strictly dependent on the tumor type and further suggests that MKK3 could represent an efficient putative molecular target that requires contextualization within a specific tumor type in order to adequately evaluate its potential effectiveness in designing novel anticancer therapies.

show abstract

DUSP1 induces paclitaxel resistance through the regulation of p-glycoprotein expression in human ovarian cancer cells

Cited by 16 publications

References 23 publications

Bioinformatics analysis to screen the key prognostic genes in ovarian cancer

Bioinformatics analysis to screen the key prognostic genes in ovarian cancer

Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis

Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword?

Contact Info

Product

Resources

About