Id proteins at the cross-road of development and cancer

Lasorella, Anna; Uo, Takuma; Iavarone, Antonio

doi:10.1038/sj.onc.1205093

Cited by 239 publications

(231 citation statements)

References 61 publications

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“…Among other members, Id2 was found to play a crucial role in the regulation of differentiation, cell cycle and proliferation in epithelial cells. It acts as a dominant negative antagonist of Rb and abrogates the tumor suppressor function of Rb, thereby promoting entry into S phase and cell proliferation (Lasorella et al, 2001(Lasorella et al, , 2005.…”

Section: Discussionmentioning

confidence: 99%

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

et al. 2007

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We investigated the effect of all-trans-retinoic acid (atRA) on proliferation in several human skin cell lines and found that antiproliferative potency of atRA correlated with the endogenous activity of canonical Wnt signaling. In HaCaT keratinocytes, we found that atRA significantly suppressed the expression of Id2, a member of the inhibitor of differentiation family of transcription factors that regulate cell growth and differentiation. However, no apparent change in the expression of other Wnt targets, like c-Myc or cyclin D1, was observed. Retinoid-induced Id2 gene suppression was associated with decreased levels of histone H3 and H4 acetylation and histone H3 Lys-4 methylation, and with recruitment of the LSD1 demethylase at the Wnt-response element (WRE) (TCF/LEF-binding site), in the Id2 gene promoter. None of such changes was detected at the WRE of c-Myc and cyclin D1 gene promoters. Inhibition of Id2 by short interfering RNA (siRNA) had a similar effect on the proliferation of HaCaT cells as exposure to atRA, whereas anti-b-catenin siRNA significantly inhibited its antiproliferative effect. These data suggest that downregulation of Id2 gene expression through transcriptional convergence between Wnt and retinoid signaling pathways underlies the antiproliferative effect of retinoids in keratinocytes, and provide evidence of gene-targeted crosstalk between signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

et al. 2007

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“…35,36 Over expression of ID1 and ID2 was shown to mediate cellular transformation 37 and is re-quired to maintain the malignant phenotype of neuroblastoma tumor cells. 38,39 Furthermore, ID2 was recently identified as a target gene of the EWS-FLI1 fusion protein. 33 An interesting group of EWS-specific markers is represented by the DNA-binding proteins CAAT/enhancer binding protein beta (CEBPB) and CBP/p300-interacting transactivator (CITED2).…”

Section: Differentiation-related Genes Specific For Ewsmentioning

confidence: 99%

Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma

Baer

Nees

Breit

et al. 2004

Intl Journal of Cancer

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Using Affymetrix oligonucleotide microarrays, we analyzed mRNA gene expression patterns of 12 primary pediatric rhabdomyosarcomas (RMS) and 11 Ewing's sarcomas (EWS), which belong to the small round blue cell tumors (SRBCTs). Diagnostic classification of these cancers is frequently complicated by the highly similar appearance in routine histology, and additional molecular markers could significantly improve tumor classification. A combination of three independent statistical approaches (t-test, SAM, k-nearest neighborhood analysis) resulted in 101 highly significant probe sets that clearly discriminate between EWS and RMS. We identified novel marker transcripts that have not been previously associated with either RMS or EWS yet, including CITED2, glypican 3 (GPC3), and cyclin D1 (CCND1). Expression levels for selected candidate genes were validated by quantitative real-time reverse-transcription PCR. Furthermore, to identify biologically meaningful trends, functional annotations were assigned to 946 genes differentially expressed between EWS and RMS (t-test). Genes involved in protein biosynthesis (n ‫؍‬ 28) and complex assembly (n ‫؍‬ 9), lipid metabolism (n ‫؍‬ 23), energy generation (n ‫؍‬ 22), and mRNA processing (n ‫؍‬ 11) were expressed significantly higher in EWS. Thus, functional annotation of tumor-specific genes reveals detailed insights into tumor biology and differentiation-specific expression patterns and gives important clues related to the possible cellular origin of these pediatric tumors. Small round blue cell tumors (SRBCTs) are frequently difficult to distinguish by standard histology or, sometimes, even by immunohistochemistry. Rhabdomyosarcoma (RMS) and Ewing's sarcomas (EWS) are common pediatric solid tumors that belong to this group that also includes neuroblastoma and Burkitt's lymphoma. However, the correct diagnosis of SRBCT tumors is essential since treatment regimens, response to therapy and prognosis may differ markedly. Therefore, molecular techniques are increasingly implemented for the diagnostic distinction of SRBCT tumors, including EWS and RMS. Progress in recent years includes the identification of characteristic tumor-specific chromosomal translocations, resulting in the expression of aberrant, oncogenic fusion proteins.RMS is the most common pediatric soft tissue sarcoma and can be histologically subdivided into the more prevalent embryonal (eRMS) and the more aggressive alveolar rhabdomyosarcoma (aRMS). ARMS have an unfavorable prognosis due to a tendency to early relapses and frequent failure of chemotherapy. This is reflected by 5-year survival rates ranging between 20 -50%. Most aRMS express PAX3-FKHR or PAX7-FKHR fusion proteins resulting from [t(2;13)(q35;q14)] or [t(1;13)(p36;q14)] translocations, respectively. 1-3 Although a frequently affected chromosomal locus in eRMS has been defined (11p15.5), specific gene(s) or a fusion transcript have not been identified. 4 Ewing's sarcomas (EWS) and the related, more differentiated peripheral neuroectodermal tumors (PNET) are...

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“…ID1 is frequently overexpressed in human cancer and associated with aggressive tumor phenotypes (Fong et al, 2004). Repression of ID1 decreased the growth of early tumors in animal models (Lyden et al, 1999;Lasorella et al, 2001). We recently showed that ID1 is frequently overexpressed in human lung adenocarcinoma, accompanied by overexpression of Src and MMP9 (Rothschild et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma

et al. 2012

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Id proteins at the cross-road of development and cancer

Cited by 239 publications

References 61 publications

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma

MicroRNA-29b is involved in the Src-ID1 signaling pathway and is dysregulated in human lung adenocarcinoma

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