Down-regulation of Ras-related Protein Rab 5C-dependent Endocytosis and Glycolysis in Cisplatin-resistant Ovarian Cancer Cell Lines

Jin, Lixu; Huo, Yi; Zheng, Zhong; Jiang, Xiaoyong; Deng, Hongbo; Chen, Yuling; Lian, Qingquan; Ge, Ren‐Shan; Deng, Haiteng

doi:10.1074/mcp.m113.033217

Cited by 40 publications

(29 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Downregulation of vimentin was identified in widely used drug resistant ovarian cancer cell lines in the present and previous studies [14, 23], suggesting that the low expression of vimentin correlated with drug resistance in ovarian cancer cells. Silencing of vimentin expression in A2780, HO-8910-PM and HO-8910 cells resulted in markedly increase the cell resistance to cisplatin further demonstrating that vimentin mediates drug resistance in ovarian cancer cells (Figure 2(f, i), Supplementary Figure S1f).…”

Section: Discussionsupporting

confidence: 71%

See 1 more Smart Citation

Downregulation of vimentin expression increased drug resistance in ovarian cancer cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

Cisplatin and other platinum-based drugs have been widely used in the treatment of ovarian cancer, but most patients acquire the drug resistance that greatly compromises the efficacy of drugs. Understanding the mechanism of drug resistance is important for finding new therapeutic approaches. In the present study, we found that the expression of vimentin was downregulated in drug-resistant ovarian cancer cell lines A2780-DR and HO-8910 as compared to their respective control cells. Overexpression of vimentin in A2780-DR cells markedly increased their sensitivity to cisplatin, whereas knockdown of vimentin in A2780, HO-8910-PM and HO-8910 cells increased the resistance to cisplatin, demonstrating that vimentin silencing enhanced cisplatin resistance in ovarian cancer cells. Quantitative proteomic analysis identified 95 differentially expressed proteins between the vimentin silenced A2780 cells (A2780-VIM-KN) and the control cells, in which downregulation of endocytic proteins and the upregulation of exocytotic proteins CHMP2B and PDZK1 were proposed to contribute the decreased cisplatin accumulation in vimentin knockdown cells. Silencing of vimentin induced upregulation of cancer stem cell markers and both A2780-DR and A2780-VIM-KN cells were more facile to form spheroids than control cells under serum-free culture condition. Our results also revealed that vimentin knockdown increased the 14-3-3 mediated retention of Cdc25C in the cytoplasm, leading to inactivation of Cdk1 and the prolonged G2 phase arrest that allowed the longer period of time for cells to repair cisplatin-damaged DNA. Taken together, we demonstrated that vimentin silencing enhanced cells' resistance to cisplatin via prolonged G2 arrest and increased exocytosis, suggesting that vimentin is a potential target for treatment of drug resistant ovarian cancer.

show abstract

Section: Discussionsupporting

confidence: 71%

“…Our previous study showed that vimentin was downregulated in drug resistant ovarian cancer cell line A2780-DR [14]. Vimentin, a member of the intermediate filament (IF) family, is ubiquitously expressed in mesenchymal cells.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of vimentin expression increased drug resistance in ovarian cancer cells

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…The standard first-line treatment for EOC is primarily cytoreductive surgery (CRS) followed by platinum-based chemotherapy [3]. However, the efficacy of chemotherapy is limited, for approximately 25% of patients relapse within six months and the overall five-year survival rate is about 30% [4]. Therefore, it’s imperative to find useful clinical markers to predict chemosensitivity of cisplatin in EOC and to decrease the failure of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway

Liu

Mei

Tian

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Rap1 interacting factor 1 (RIF1) was deemed to be involved in replication timing regulation and DNA damage response. However, little is known about the role of RIF1 in malignancies. Thus, this study aimed to investigate whether the expression of RIF1 is relevant to the response of epithelial ovarian cancer (EOC) patients to cisplatin chemotherapy and its underlying mechanism. Methods: Immunohistochemistry was used for detecting the expression of RIF1 in 72 human ovarian cancer tissues followed by association analysis of RIF1 expression with patients’ responses to platinum-based chemotherapy. The survival analysis of ovarian patients based on platinum chemotherapy was analyzed using online databases. RNA interference of RIF1 was carried out in OVCAR3 and A2780 cell lines, to determine the effect of lacking RIF1 expression on cellular responses to cisplatin by using MTS assay. The nucleotide excision repair (NER) capacity of these cells was assessed by using host-cell reactivation and UV sensitivity assay. Western Blot analysis was carried out to determine the effect of RIF1 on the proteins of NER and apoptosis signaling pathway by using RIF1 knockdown cells. BALB/c nude mice model was used for detection of response to cisplatin in vivo. Results: RIF1 expression was significantly associated with the response of ovarian patients to platinum-based chemotherapy (P< 0.01). In cohorts from online databases, high expression of RIF1 was associated with higher mortality of EOC patients based on platinum chemotherapy (P < 0.01). RIF1 knockdown increased sensitivity to cisplatin in EOC in vitro and in vivo. Deletion of RIF1 impaired the NER activity by inhibiting the NER proteins in ovarian cancer cells. Besides, knockdown of RIF1 enhanced cisplatin-induced apoptosis. Conclusions: RIF1 plays an important role in regulating the expression of NER proteins, which in turn contributes to cellular response to cisplatin and EOC patients’ response to platinum-based chemotherapy. RIF1 knockdown also promotes cisplatin-induced apoptosis. RIF1 may serve as a novel biomarker for predicting platinum-based chemosensitivity and the prognosis of EOC patients.

show abstract

“…LC-MS/MS was performed as described previously [28] with slight modifications. Briefly, the samples were resolved using an Acclaim PepMap RSLC column on a Thermo Scientific UltiMate 3000 RSLCnano System.…”

Section: Methodsmentioning

confidence: 99%

Quantitative proteomics reveals that distant recurrence-associated protein R-Ras and Transgelin predict post-surgical survival in patients with Stage III colorectal cancer

Gao

Chen

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Surgical resection supplemented with adjuvant chemotherapy is the current preferred treatment for Stage III colorectal cancer (CRC). However, as many as 48% of patients who undergo curative resection eventually suffer from incurable distant recurrence. To investigate the molecular mechanisms involved in Stage III CRC post-surgical distant recurrence, we identified a total of 146 differentially expressed proteins (DEPs) associated with distant recurrence in Stage III CRC using TMT-based quantitative mass spectrometry. Among these DEPs, the altered expressions of R-Ras and Transgelin were then validated in 192 individual specimens using immunohistochemistry (IHC). Furthermore, Kaplan-Meier analysis revealed that the levels of R-Ras and Transgelin were significantly associated with 5-year overall survival (OS) and disease-free survival (DFS), and multivariate Cox-regression analyses revealed that R-Ras and Transgelin were independent prognostic factors for OS and DFS, respectively. In conclusion, this study identified potential biochemical players involved in distant recurrence and indicates that R-Ras and Transgelin are potential post-surgical prognostic biomarkers for Stage III CRC. This proteomics data have been submitted to Proteome Xchange under accession number PXD002903.

show abstract

Down-regulation of Ras-related Protein Rab 5C-dependent Endocytosis and Glycolysis in Cisplatin-resistant Ovarian Cancer Cell Lines

Cited by 40 publications

References 49 publications

Downregulation of vimentin expression increased drug resistance in ovarian cancer cells

Downregulation of vimentin expression increased drug resistance in ovarian cancer cells

Downregulation of RIF1 Enhances Sensitivity to Platinum-Based Chemotherapy in Epithelial Ovarian Cancer (EOC) by Regulating Nucleotide Excision Repair (NER) Pathway

Quantitative proteomics reveals that distant recurrence-associated protein R-Ras and Transgelin predict post-surgical survival in patients with Stage III colorectal cancer

Contact Info

Product

Resources

About