Proteomics

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SILAC-Based Quantitative Proteomics Identifies Multifactorial Mechanism of Oxaliplatin Resistance in Pancreatic Cancer Cells


ABSTRACT: Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of pancreatic cancer. Understanding the cellular mechanisms of oxaliplatin resistance is important for developing new strategies to overcome drug resistance in pancreatic cancer. In this study, we performed a stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics analysis of oxaliplatin-resistant and sensitive pancreatic cancer PANC-1 cells. We identified 107 proteins whose expression levels changed between oxaliplatin-resistant and sensitive cells, which were involved in multiple biological processes, including DNA repair, drug response, apoptotic signalling, and the type 1 interferon signalling pathway. Notably, myristoylated alanine-rich C-kinase substrate (MARCKS) and wntless homolog protein (WLS) were upregulated in oxaliplatin-resistant cells compared to sensitive cells, as confirmed by qRT-PCR and Western blot analysis. We further demonstrated the activation of AKT and β-catenin signalling (downstream targets of MARCKS and WLS, respectively) in oxaliplatin-resistant PANC-1 cells. Additionally, we show that the siRNA-mediated suppression of both MARCKS and WLS enhanced oxaliplatin sensitivity in oxaliplatin-resistant PANC-1 cells. Taken together, our results provide insights into multiple mechanisms of oxaliplatin resistance in pancreatic cancer cells and reveal that MARCKS and WLS might be involved in the chemotherapeutic resistance in pancreatic cancer.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pancreatic Ductal Adenocarcinoma Cell Line

SUBMITTER: Youn Eun Kim  

LAB HEAD: Dukjin Kang

PROVIDER: PXD021251 | Pride | 2021-09-09

REPOSITORIES: Pride

Dataset's files

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Action DRS
180821_PANC1_P5OX50_0mM.raw Raw
180821_PANC1_P5OX50_1000mM.raw Raw
180821_PANC1_P5OX50_100mM.raw Raw
180821_PANC1_P5OX50_15mM.raw Raw
180821_PANC1_P5OX50_20mM.raw Raw
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Publications

SILAC-Based Quantitative Proteomic Analysis of Oxaliplatin-Resistant Pancreatic Cancer Cells.

Kim Young Eun YE   Kim Eun-Kyung EK   Song Min-Jeong MJ   Kim Tae-Young TY   Jang Ho Hee HH   Kang Dukjin D  

Cancers 20210210 4


Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of pancreatic cancer. Understanding the cellular mechanisms of oxaliplatin resistance is important for developing new strategies to overcome drug resistance in pancreatic cancer. In this study, we performed a stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics analysis of oxaliplatin-resistant and sensitive pancreatic cancer PANC-1 cells. We identified 107 proteins whose expression le  ...[more]

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