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• W2886811891 abstract "Label-retaining cancer cells (LRCC) have been proposed as a model of slowly cycling cancer stem cells (CSC) which mediate resistance to chemotherapy, tumor recurrence, and metastasis. The molecular mechanisms of chemoresistance in LRCC remain to-date incompletely understood. This study aims to identify molecular targets in LRCC that can be exploited to overcome resistance to gemcitabine, a standard chemotherapy agent for the treatment of pancreas cancer. LRCC were isolated following Cy5-dUTP staining by flow cytometry from pancreatic cancer cell lines. Gene expression profiles obtained from LRCC, non-LRCC (NLRCC), and bulk tumor cells were used to generate differentially regulated pathway networks. Loss of upregulated targets in LRCC on gemcitabine sensitivity was assessed via RNAi experiments and pharmacological inhibition. Expression patterns of PDPK1, one of the upregulated targets in LRCC, was studied in patients’ tumor samples and correlated with pathological variables and clinical outcome. LRCC are significantly more resistant to gemcitabine than the bulk tumor cell population. Non-canonical EGF (epidermal growth factor)-mediated signal transduction emerged as the top upregulated network in LRCC compared to non-LRCC, and knock down of EGF signaling effectors PDPK1 (3-phosphoinositide dependent protein kinase-1), BMX (BMX non-receptor tyrosine kinase), and NTRK2 (neurotrophic receptor tyrosine kinase 2) or treatment with PDPK1 inhibitors increased growth inhibition and induction of apoptosis in response to gemcitabine. Knockdown of PDPK1 preferentially increased growth inhibition and reduced resistance to induction of apoptosis upon gemcitabine treatment in the LRCC vs non-LRCC population. These findings are accompanied by lower expression levels of PDPK1 in tumors compared to matched uninvolved pancreas in surgical resection specimens and a negative association of membranous localization on IHC with high nuclear grade (p < 0.01). Pancreatic cancer cell-derived LRCC are relatively resistant to gemcitabine and harbor a unique transcriptomic profile compared to bulk tumor cells. PDPK1, one of the members of an upregulated EGF-signaling network in LRCC, mediates resistance to gemcitabine, is found to be dysregulated in pancreas cancer specimens, and might be an attractive molecular target for combination therapy studies." @default.
• W2886811891 created "2018-08-22" @default.
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• W2886811891 date "2018-07-31" @default.
• W2886811891 modified "2023-10-14" @default.
• W2886811891 title "Loss of PDPK1 abrogates resistance to gemcitabine in label-retaining pancreatic cancer cells" @default.
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• W2886811891 cites W1965406763 @default.
• W2886811891 cites W1968812902 @default.
• W2886811891 cites W1971095929 @default.
• W2886811891 cites W1979394897 @default.
• W2886811891 cites W1983180681 @default.
• W2886811891 cites W1984483719 @default.
• W2886811891 cites W1986619013 @default.
• W2886811891 cites W1990311482 @default.
• W2886811891 cites W1992649924 @default.
• W2886811891 cites W1999025078 @default.
• W2886811891 cites W2004878973 @default.
• W2886811891 cites W2008878539 @default.
• W2886811891 cites W2009094422 @default.
• W2886811891 cites W2019264784 @default.
• W2886811891 cites W2023427658 @default.
• W2886811891 cites W2024424959 @default.
• W2886811891 cites W2030151785 @default.
• W2886811891 cites W2031348772 @default.
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• W2886811891 cites W2074371275 @default.
• W2886811891 cites W2074956041 @default.
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• W2886811891 cites W2134391588 @default.
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• W2886811891 doi "https://doi.org/10.1186/s12885-018-4690-1" @default.
• W2886811891 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6069886" @default.
• W2886811891 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30064387" @default.
• W2886811891 hasPublicationYear "2018" @default.
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