Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy

Stratford, Anna L.; Habibi, Golareh; Astanehe, Arezoo; Jiang, Helen; Hu, Kaiji; Park, Eugene; Shadeo, Ashleen; Buys, Timon P.H.; Lam, Wan L.; Pugh, Trevor J.; Marra, Marco A.; Nielsen, Torsten O.; Klinge, U.; Mertens, Peter R.; Aparicio, Samuel; Dunn, Sandra E.

doi:10.1186/bcr1767

Cited by 132 publications

(140 citation statements)

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“…The Lightshift Chemiluminescent EMSA kit (Pierce Biotechnology) was used to perform EMSAs using oligonucleotides corresponding to potential YB-1 binding sites according to our earlier published methods (Stratford et al, 2007). Briefly, binding reactions contained 1 Â binding buffer, 50 ng/ml poly dIdC, 20 fmol biotin-labeled double stranded DNA and 6 mg nuclear extract.…”

Section: Emsamentioning

confidence: 99%

“…After 96 h cells were harvested. Small inhibitory RNAs targeting YB-1, referred to as siYB-1 #2 and siYB-1 #3, were obtained from Dharmacon (Lafayette, CO, USA) as described earlier (Stratford et al, 2007) and Qiagen (Catalog number SI03019191), respectively. The siMET oligonucleotide was obtained from Qiagen (Catalog number SI00604821).…”

Section: Emsamentioning

confidence: 99%

“…Therefore, much effort is now focused on identifying new molecular targets in BLBCs. One target of current interest is the transcription/translation factor Y-box binding protein-1 (YB-1) because of its documented high expression in approximately 70% of BLBCs (Stratford et al, 2007) and its association with poor survival (Habibi et al, 2008). YB-1 is consistently associated with high rates of relapse in virtually all breast cancer subtypes including BLBC (Habibi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that such YB-1-mediated activation of EGFR transcription also promotes the growth of BLBCs (Wu et al, 2006). The induction of EGFR expression is dependent on phosphorylation of YB-1 at S102 (Wu et al, 2006;Stratford et al, 2007), which is achieved by serine/threonine kinases Akt (Sutherland et al, 2005) or RSK (Stratford et al, 2008) leading to nuclear translocation. Importantly, nuclear YB-1 has been reported in many instances to be a universal biomarker for drug resistance, thus understanding how it regulates gene expression is essential (Kuwano et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells

et al. 2009

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Basal-like breast cancers (BLBCs) are aggressive tumors with high relapse rates and poor survival. We recently reported that >70% of primary BLBCs express the oncogenic transcription/translation factor Y-box binding protein-1 (YB-1) and silencing it with small interfering RNAs (siRNAs) attenuates the growth of BLBC cell lines. To understand the basis of these earlier findings, we profiled YB-1:DNA complexes by chromatin immunoprecipitation (ChIP)-on-chip. Several tumor growth-promoting genes such as MET, CD44, CD49f, WNT and NOTCH family members were identified. In addition, YB-1 and MET are coordinately expressed in BLBC cell lines, as well as in normal human mammary progenitor cells. MET was confirmed to be a YB-1 target through traditional ChIP and gel-shift assays. More specifically, YB-1 binds to À1018 bp on the MET promoter. Silencing YB-1 with siRNA decreased MET promoter activity, transcripts, as well as protein levels and signaling. Conversely, expressing wild-type YB-1 or a constitutively active mutant YB-1 (D102) increased MET expression. Finally, silencing YB-1 or MET attenuated anchorageindependent growth of BLBC cell lines. Together, these findings implicate MET as a target of YB-1 that work in concert to promote BLBC growth.

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Section: Emsamentioning

confidence: 99%

Section: Emsamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells

et al. 2009

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“…The BLBC specimens and MDA-MB-231 were assayed using an SMRT aCGH platform as previously described (Shadeo and Lam, 2006;Stratford et al, 2007). To be classified as gain, there has to be a probability >80% (determined by Hidden Markov Model algorithm) and >0.15 log 2 ratio (determined by aCGH-Smooth software).…”

Section: Immunoblotsmentioning

confidence: 99%

The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1

et al. 2009

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YB‐1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

et al. 2023

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Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y‐box‐binding protein‐1 (YB‐1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB‐1 on target gene regulation and PM cell behavior. Whereas siRNA‐mediated YB‐1 knockdown reduced cell motility, YB‐1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB‐1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB‐1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB‐1. Finally, we identified snail as a critical regulator of YB‐1‐mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB‐1 in this cancer. In this context, we found that YB‐1 closely regulates EGFR and snail, and, moreover, that YB‐1‐induced cell migration depends on snail.

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Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy

Cited by 132 publications

References 50 publications

Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells

Profiling YB-1 target genes uncovers a new mechanism for MET receptor regulation in normal and malignant human mammary cells

The transcriptional induction of PIK3CA in tumor cells is dependent on the oncoprotein Y-box binding protein-1

YB‐1 regulates mesothelioma cell migration via snail but not EGFR, MMP1, EPHA5 or PARK2

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