v-src induces cisplatin resistance by increasing the repair of cisplatin-DNA interstrand cross-links in human gallbladder adenocarcinoma cells

Masumoto, Naoko; Nakano, Susumu; Fujishima, Hiromitsu; Kohno, Kimitoshi; Niho, Yoshiyuki

doi:10.1002/(sici)1097-0215(19990301)80:5<731::aid-ijc17>3.0.co;2-h

Cited by 51 publications

(18 citation statements)

References 26 publications

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“…Activated Src has also been shown to cause cancer cells to be resistant to various chemotherapeutic agents and targeted therapeutics [50, 51]. Actually, numerous reports have demonstrated that Src activation is involved in drug resistance by enhancing DNA repair [25–27]. Our present results showing that cisplatin treatment significantly increased the levels of pSrc Y416 (activated Src) as well as pEGFR Y845 in KB cells but not in P-gp overexpressed KBvin10 cells.…”

Section: Discussionsupporting

confidence: 57%

“…Several reports have identified associations between Src and resistance to irradiation, cisplatin, and paclitaxel [17, 23, 24]. Src activation-induced drug resistance is likely because of the activation of DNA-PK and enhancement of DNA double-strand break repair [25–27]. In addition, Src causes the dissociation of cyclin-dependent kinase 2 from cyclin A and induces S-phase arrest, thereby enhancing the repair of etoposide-induced DNA damage [28].…”

Section: Introductionmentioning

confidence: 99%

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P-glycoprotein attenuates DNA repair activity in multidrug-resistant cells by acting through the Cbp-Csk-Src cascade

Lin

Pidugu

et al. 2017

Oncotarget

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

P-glycoprotein attenuates DNA repair activity in multidrug-resistant cells by acting through the Cbp-Csk-Src cascade

Lin

Pidugu

et al. 2017

Oncotarget

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“…Several studies have linked the expression of v-Src and other Src family kinases to resistance of a variety of chemotherapeutic agents including cisplatin, geftinib, paclitaxel, oxaliplatin and tamoxifen [93-97]. Since chemoresistance is often associated with increased cell motility and invasiveness, it has been suggested that v-Src controls these activities by inducing the epithelial-to-mesenchymal transition (EMT) in tumor cells [8].…”

Section: Discussionmentioning

confidence: 99%

Cellular processes of v-Src transformation revealed by gene profiling of primary cells - Implications for human cancer

Maslikowski

Neel

et al. 2010

BMC Cancer

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BackgroundCell transformation by the Src tyrosine kinase is characterized by extensive changes in gene expression. In this study, we took advantage of several strains of the Rous sarcoma virus (RSV) to characterize the patterns of v-Src-dependent gene expression in two different primary cell types, namely chicken embryo fibroblasts (CEF) and chicken neuroretinal (CNR) cells. We identified a common set of v-Src regulated genes and assessed if their expression is associated with disease-free survival using several independent human tumor data sets.MethodsCEF and CNR cells were infected with transforming, non-transforming, and temperature sensitive mutants of RSV to identify the patterns of gene expression in response to v-Src-transformation. Microarray analysis was used to measure changes in gene expression and to define a common set of v-Src regulated genes (CSR genes) in CEF and CNR cells. A clustering enrichment regime using the CSR genes and two independent breast tumor data-sets was used to identify a 42-gene aggressive tumor gene signature. The aggressive gene signature was tested for its prognostic value by conducting survival analyses on six additional tumor data sets.ResultsThe analysis of CEF and CNR cells revealed that cell transformation by v-Src alters the expression of 6% of the protein coding genes of the genome. A common set of 175 v-Src regulated genes (CSR genes) was regulated in both CEF and CNR cells. Within the CSR gene set, a group of 42 v-Src inducible genes was associated with reduced disease- and metastasis-free survival in several independent patient cohorts with breast or lung cancer. Gene classes represented within this group include DNA replication, cell cycle, the DNA damage and stress responses, and blood vessel morphogenesis.ConclusionBy studying the v-Src-dependent changes in gene expression in two types of primary cells, we identified a set of 42 inducible genes associated with poor prognosis in breast and lung cancer. The identification of these genes provides a set of biomarkers of aggressive tumor behavior and a framework for the study of cancer cells characterized by elevated Src kinase activity.

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“…Also, in ovarian cancer cells with constitutively active Src, treatment with pharmacological inhibitors of Src triggered a reduction in tumor cell survival after cisplatin exposure [18]. In addition, v-Src induced cisplatin resistance by promoting repair of cisplatin-DNA adducts in adenocarcinoma cells [51]. The variable requirements for Src may be attributed to differences in the experimental approaches.…”

Section: Discussionmentioning

confidence: 99%

Carcinoma Matrix Controls Resistance to Cisplatin through Talin Regulation of NF-kB

et al. 2011

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Extracellular matrix factors within the tumor microenvironment that control resistance to chemotherapeutics are poorly understood. This study focused on understanding matrix adhesion pathways that control the oral carcinoma response to cisplatin. Our studies revealed that adhesion of HN12 and JHU012 oral carcinomas to carcinoma matrix supported tumor cell proliferation in response to treatment with cisplatin. Proliferation in response to 30 µM cisplatin was not observed in HN12 cells adherent to other purified extracellular matrices such as Matrigel, collagen I, fibronectin or laminin I. Integrin β1 was important for adhesion to carcinoma matrix to trigger proliferation after treatment with cisplatin. Disruption of talin expression in HN12 cells adherent to carcinoma matrix increased cisplatin induced proliferation. Pharmacological inhibitors were used to determine signaling events required for talin deficiency to regulate cisplatin induced proliferation. Pharmacological inhibition of NF-kB reduced proliferation of talin-deficient HN12 cells treated with 30 µM cisplatin. Nuclear NF-kB activity was assayed in HN12 cells using a luciferase reporter of NF-kB transcriptional activity. Nuclear NF-kB activity was similar in HN12 cells adherent to carcinoma matrix and collagen I when treated with vehicle DMSO. Following treatment with 30 µM cisplatin, NF-kB activity is maintained in cells adherent to carcinoma matrix whereas NF-kB activity is reduced in collagen I adherent cells. Expression of talin was sufficient to trigger proliferation of HN12 cells adherent to collagen I following treatment with 1 and 30 µM cisplatin. Talin overexpression was sufficient to trigger NF-kB activity following treatment with cisplatin in carcinoma matrix adherent HN12 cells in a process disrupted by FAK siRNA. Thus, adhesions within the carcinoma matrix create a matrix environment in which exposure to cisplatin induces proliferation through the function of integrin β1, talin and FAK pathways that regulate NF-kB nuclear activity.

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v-src induces cisplatin resistance by increasing the repair of cisplatin-DNA interstrand cross-links in human gallbladder adenocarcinoma cells

Cited by 51 publications

References 26 publications

P-glycoprotein attenuates DNA repair activity in multidrug-resistant cells by acting through the Cbp-Csk-Src cascade

P-glycoprotein attenuates DNA repair activity in multidrug-resistant cells by acting through the Cbp-Csk-Src cascade

Cellular processes of v-Src transformation revealed by gene profiling of primary cells - Implications for human cancer

Carcinoma Matrix Controls Resistance to Cisplatin through Talin Regulation of NF-kB

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