Id proteins in cell growth and tumorigenesis

Sikder, Hashmat; Devlin, Meghann K; Dunlap, Shariff; Ryu, Byungwoo; Alani, Rhoda M.

doi:10.1016/s1535-6108(03)00141-7

Cited by 282 publications

(289 citation statements)

References 47 publications

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“…Ectopic expression of Id proteins abrogates differentiation and can lead to cellular immortalization. In clinical studies, expression of members of the Id family significantly correlated both with cancer progression and overall prognosis, implying an important role of these regulatory proteins in carcinogenesis (Sikder et al, 2003). Among other members, Id2 was found to play a crucial role in the regulation of differentiation, cell cycle and proliferation in epithelial cells.…”

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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“…Id protein family is a group of helix -loop -helix transcription factors that have been implicated in different steps in carcinogenesis such as tumorigenesis, differentiation and metastasis (Benezra et al, 2001;Zebedee and Hara, 2001;Hasskarl and Munger, 2002;Sikder et al, 2003;Fong et al, 2004;Wong et al, 2004). Recent studies exploring the potential use of Id proteins as tumour markers have revealed that they play different roles in different types of cancer such that they might act as markers for progression, metastasis and prognosis in some cancer types.…”

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confidence: 99%

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Chan

et al. 2007

Br J Cancer

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Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix -loop -helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P ¼ 0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P ¼ 0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P ¼ 0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients.

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“…They promote cell growth, inhibit differentiation, and play critical roles in development and cancer (Lasorella et al, 2001). Expression of Id proteins is increased in a large variety of human tumors, including cutaneous squamous cell carcinoma and basal cell carcinoma (Langlands et al, 2000;Chaturvedi et al, 2003;Sikder et al, 2003). In addition, enhanced levels of Id1 were detected in biopsies from lesioned psoriatic skin, suggesting a regulatory role of this protein family in keratinocyte proliferation and differentiation (Bjorntorp et al, 2003).…”

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confidence: 99%

Id proteins: Novel targets of activin action, which regulate epidermal homeostasis

et al. 2005

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Activin is a member of the transforming growth factor b (TGF-b) family, which plays a crucial role in skin morphogenesis and wound healing. To gain insight into the underlying mechanisms of action, we searched for activin-regulated genes in cultured keratinocytes. One of the identified target genes encodes Id1, a negative regulator of helix-loop-helix transcription factors. We show that Id1, Id2, and Id3 are strongly downregulated by activin in keratinocytes in vitro and in vivo. To determine the role of Id1 in keratinocyte biology, we generated stable HaCaT keratinocyte cell lines overexpressing this protein. Our results revealed that enhanced levels of Id1 do not affect proliferation of keratinocytes in monoculture under exponential culture conditions or in response to activin or TGF-b1. However, in three-dimensional organotypic cultures, Id1-overexpressing HaCaT cells formed a hyperthickened and disorganized epithelium that was characterized by enhanced keratinocyte proliferation, abnormal differentiation, and an increased rate of apoptosis. These results identify an important function of Id1 in the regulation of epidermal homeostasis.

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Id proteins in cell growth and tumorigenesis

Cited by 282 publications

References 47 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

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Id proteins: Novel targets of activin action, which regulate epidermal homeostasis

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