CIP2A expression is increased in prostate cancer

Vaarala, Markku H.; Väisänen, Marja-Riitta; Ristimäki, Ari

doi:10.1186/1756-9966-29-136

Cited by 84 publications

(58 citation statements)

References 11 publications

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“…Moreover, CIP2A expression predicts poor patient prognosis in certain gastric cancer subtypes and in non-small cell lung cancer (Khanna et al, 2009;Dong et al, 2010). In breast cancer, CIP2A expression correlates with disease aggressiveness and in prostate cancer with a high Gleason's score (Come et al, 2009;Vaarala et al, 2010). Taken together, these studies have firmly established CIP2A as a novel, clinically relevant human oncoprotein.…”

Section: Introductionmentioning

confidence: 59%

“…CIP2A depletion results in inhibition of malignant cell growth and inhibition of tumor growth in mouse xenograft models (Junttila et al, 2007;Come et al, 2009). CIP2A is overexpressed in most major solid human cancer types, including head and neck squamous cell carcinomas as well as gastric, esophageal, breast, colon, lung and prostate cancer (Junttila et al, 2007;Li et al, 2008;Come et al, 2009;Khanna et al, 2009;Dong et al, 2010;Katz et al, 2010;Qu et al, 2010;Vaarala et al, 2010). Strikingly, with the exception of breast cancer, in which 40% of patient samples overexpress CIP2A (Come et al, 2009), all other studied human cancer types have CIP2A overexpression in 65-90% of patient samples.…”

Section: Introductionmentioning

confidence: 99%

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CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes

et al. 2012

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Protein phosphatase 2A (PP2A) is a critical human tumor-suppressor complex. A recently characterized PP2A inhibitor protein, namely cancerous inhibitor of PP2A (CIP2A), has been found to be overexpressed at a high frequency in most of the human cancer types. However, our understanding of gene expression programs regulated by CIP2A is almost absent. Moreover, clinical relevance of the CIP2A-regulated transcriptome has not been addressed thus far. Here, we report a high-confidence transcriptional signature regulated by CIP2A. Bioinformatic pathway analysis of the CIP2A signature revealed that CIP2A regulates several MYC-dependent and MYCindependent gene programs. With regard to MYCindependent signaling, JNK2 expression and transwell migration were inhibited by CIP2A depletion, whereas MYC depletion did not affect either of these phenotypes. Instead, depletion of either CIP2A or MYC inhibited cancer cell colony growth with statistically indistinguishable efficiency. Moreover, CIP2A depletion was shown to regulate the expression of several established MYC target genes, out of which most were MYC-repressed genes. CIP2A small-interfering RNA-elicited inhibition of colony growth or activation of MYC-repressed genes was reversed at large by concomitant PP2A inhibition. Finally, the CIP2A signature was shown to cluster with basal-type and human epidermal growth factor receptor (HER)2-positive (HER2 þ ) breast cancer signatures. Accordingly, CIP2A protein expression was significantly associated with basal-like (P ¼ 0.0014) and HER2 þ (Po0.0001) breast cancers. CIP2A expression also associated with MYC gene amplification (Po0.001). Taken together, identification of CIP2A-driven transcriptional signature, and especially novel MYC-independent signaling programs regulated by CIP2A, provides important resource for understanding CIP2A's role as a clinically relevant human oncoprotein. With regard to MYC, these results both validate CIP2A's role in regulating MYC-mediated gene expression and provide a plausible novel explanation for the high MYC activity in basal-like and HER2 þ breast cancers.

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Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes

et al. 2012

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“…19 In addition to HCC, CIP2A is over-expressed in several human malignancies including gastric cancer, head and neck cancer, colon cancer, breast cancer, prostate cancer and non-small cell lung cancer. [19][20][21][22][23][24][25] Similarly, Come et al 25 found that CIP2A is associated with clinical aggressiveness in human breast cancer and promotes the malignant growth of breast cancer cells. Of note, very recently CIP2A has been found to be related to hematologic malignancies; in the first case recorded, an MLL-KIAA1524 fusion gene was identified in an infant with acute myeloid leukemia (AML).…”

Section: Introductionmentioning

confidence: 99%

Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced apoptosis in leukemia cells

Liu

Shiau²,

Kuo³

et al. 2012

Haematologica

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“…Cancerous inhibitor of PP2A (CIP2A), which is known to enhance the migration and proliferation of tumor cells, is overexpressed in various types of human cancers, including breast (Come et al 2009, Niemela et al 2012, Tseng et al 2012, Laine et al 2013, prostate (Vaarala et al 2010), lung (Dong et al 2011), pancreatic (Wang et al 2013), bladder (Huang et al 2012a), blood or bone marrow (Lucas et al 2011, colon (Teng et al 2012), ovarian (Bockelman et al 2011b), cervical (Huang et al 2010), tongue (Bockelman et al 2011a), oral (Basile & Czerninski 2010), esophageal squamous (Qu et al 2012), and head and neck squamous (Ferreira et al 2004) cancers. CIP2A expression is transcriptionally enhanced by Ets1 (Zhao et al 2010), and the concurrent binding of Ets1 and Elk1 to the proximal CIP2A promoter is absolutely required for CIP2A expression in cervical, endometrial, and liver carcinoma cell lines (Huang et al 2012b, Pallai et al 2012.…”

Section: Introductionmentioning

confidence: 99%

Estradiol enhances CIP2A expression by the activation of p70 S6 kinase

Choi¹,

Koo²,

Park³

et al. 2013

Endocrine-Related Cancer

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Cancerous inhibitor of PP2A (CIP2A) stimulates the proliferation of various cancer cells, and 17b-estradiol (E 2 ) enhances the proliferation of breast cancer cells. E 2 activates epidermal growth factor receptor (EGFR), stimulating the MEK1/2 and PI3K pathways, and CIP2A expression is increased by the MEK1/2-induced transcription factor ETS1. It is possible for E 2 to increase CIP2A expression. This study examined whether E 2 could increase CIP2A expression and whether CIP2A is highly expressed in estrogen receptor (ER)-positive breast cancer tissues. E 2 increased CIP2A expression at the translational level in a c-MYC-independent manner in MCF-7 cells. E 2 -enhanced proliferation was impaired without CIP2A expression. E 2 -stimulated EGFR activated the MAPK and PI3K pathways, which converged to activate p70 S6 kinase (S6K). Phosphorylation at all the three phosphorylation sites (S424/T421, T229, and T389) on S6K was required for the phosphorylation of eukaryotic initiation factor 4B (eIF4B), which was responsible for the increase in CIP2A translation. Furthermore, CIP2A expression was higher in ER-positive tissues than in ER-negative tissues. This is the first study, to our knowledge, to demonstrate that CIP2A is a key factor in E 2 -enhanced proliferation and that estrogen regulates CIP2A expression by non-genomic action through EGFR.

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CIP2A expression is increased in prostate cancer

Cited by 84 publications

References 11 publications

CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes

CIP2A signature reveals the MYC dependency of CIP2A-regulated phenotypes and its clinical association with breast cancer subtypes

Cancerous inhibitor of protein phosphatase 2A determines bortezomib-induced apoptosis in leukemia cells

Estradiol enhances CIP2A expression by the activation of p70 S6 kinase

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