Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer

Igal, R. Ariel

doi:10.1093/carcin/bgq131

Cited by 273 publications

(278 citation statements)

References 84 publications

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“…Furthermore, we found that UPATmediated up-regulation of these genes is required for the survival of colon cancer cells. Consistent with our results, SCD1, the main enzyme involved in the synthesis of monounsaturated fatty acids, has been shown to be required for cancer cell proliferation, survival, transformation to cancer (32), and cancer spheroids propagation (33). The Sprouty family of proteins, key regulators of ERK signaling, has been shown to be able to function as negative or positive regulators of tumor development and/or progression in a cell type-dependent manner (34).…”

Section: Discussionsupporting

confidence: 88%

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Taniue

Kurimoto

Sugimasa

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

127

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Many long noncoding RNAs (lncRNAs) are reported to be dysregulated in human cancers and play critical roles in tumor development and progression. Furthermore, it has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic loci or by controlling transcriptional or posttranscriptional processes. Here we show that an lncRNA termed UPAT [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domaincontaining protein 1 (UHRF1) Protein Associated Transcript] is required for the survival and tumorigenicity of colorectal cancer cells. UPAT interacts with and stabilizes the epigenetic factor UHRF1 by interfering with its β-transducin repeat-containing protein (TrCP)-mediated ubiquitination. Furthermore, we demonstrate that UHRF1 up-regulates Stearoyl-CoA desaturase 1 and Sprouty 4, which are required for the survival of colon tumor cells. Our study provides evidence for an lncRNA that regulates protein ubiquitination and degradation and thereby plays a critical role in the survival and tumorigenicity of tumor cells. Our results suggest that UPAT and UHRF1 may be promising molecular targets for the therapy of colon cancer.A mong the RNA products transcribed from the mammalian genome are numerous long noncoding RNAs (lncRNAs)-that is, RNAs longer than 200 nucleotides with little or no protein-coding potential (1, 2). Many lncRNAs are expressed in a developmentally regulated and cell type-dependent manner (3, 4). Increasing evidence suggests that lncRNAs play critical roles in a diverse set of biological processes, including proliferation, differentiation, embryogenesis, neurogenesis, and stem cell pluripotency (5, 6).It has been reported that many lncRNAs regulate gene expression by recruiting chromatin remodeling complexes to specific genomic regions (2). It has also been shown that many lncRNAs regulate transcription by modulating the activity of transcriptional regulators (1, 6-8). lncRNAs also regulate various posttranscriptional processes, including splicing, transport, translation, and degradation of mRNA. Furthermore, recent studies have shown that a number of lncRNAs play critical roles in tumor development and progression.UHRF1 [ubiquitin-like plant homeodomain (PHD) and really interesting new gene (RING) finger domain-containing protein 1] is an epigenetic factor that consists of multiple domains (9). UHRF1 regulates transcription by regulating DNA methylation and histone modification. UHRF1 also possesses E3 ubiquitin ligase activity and ubiquitinates histones and DNA methyltransferase 1 (DNMT1), thereby regulating the chromatin structure and stability of DNMT1 (10, 11). UHRF1 plays key roles in multiple biological processes, including proliferation and development. Furthermore, UHRF1 is overexpressed in various tumors, including colon, breast, bladder, prostate, and lung cancers, and plays a critical role in the proliferation and survival of tumor cells (9).In the present study, we attempted to identify lncRNAs criti...

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Section: Discussionsupporting

confidence: 88%

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Taniue

Kurimoto

Sugimasa

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

127

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“…Thereby, has been proposed a relationship between SCD1 activity and tumor growth. In several types of cancers, elevated SCD1 expression and activity have been detected (34).…”

Section: Resultsmentioning

confidence: 99%

Difference in fatty acids composition of breast adipose tissue in women with breast cancer and benign breast disease

Conceição¹,

Dias²,

Pessoa³

et al. 2017

Nutr Hosp

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Introduction: Breast cancer is the second most common cancer in the world, and the most frequent cancer among women. Moreover, there are factors that influence the risk for breast cancer including the age, genetic and endocrine factors, and lifestyle.Objectives: Evaluate the consumption of fatty acids; compare the fatty acids composition in the breast adipose tissue of women with breast cancer and benign breast disease as well as potential risk factors; and describe the genotypic frequency of the Pro12Ala PPARγpolymorphism.Material and Methods: A hospital-based case-control study was conducted including incident cases (n = 38 breast cancer; n = 75 benign breast disease; n = 166 control). Lifestyle features, socioeconomic issues, dietary intake, anthropometry, and blood and tissue data were assessed.Results: No differences were observed for fatty acids intake. Interestingly, lauric acid (P = 0.001), myristic acid (P = 0.036), stearic acid (P = 0.031), and total saturated fatty acids (SFAs) (P=0.048) had lower concentrations in BC than in BBD women, while palmitoleic acid (P = 0.022), erucic acid (P = 0.002), total monounsaturated fatty acids (MUFAs) (P = 0.039) and oleic acid/stearic acid ratio (P = 0.015) increased. There was no significant association between PPARγ polymorphism and studied groups (P = 0.977). The age at first full pregnancy (P = 0.004) was significantly associated with the development BC, whereas BMI (P = 0.005); percentage of body fat (P = 0.024); physical activity (P = 0.036); and age at menarche (P = 0.008), at first full pregnancy (P < 0.001), and of first mammogram (P = 0.018) were significantly associated with the development of BBD.Conclusion: The results suggest a different fatty acids composition of breast adipose tissue, a biomarker of long-term dietary intake, particularly for SFAs, MUFA and 18: 1 n-9/18: 00 ratio. Our findings also show that are differences in the factors related to the development of BC and BBC.

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“…A growing body of evidence has recently emerged implicating the expression and activity of SCD1 in the proliferation and survival of cancer cells (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). We sought to understand whether pharmacologic inhibition of SCD1 might have therapeutic benefit in human cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a number of reports have implicated SCD1 expression and activity in the pathogenesis of cancer (for review see ref. 4). Human SCD1 mRNA was found to be overexpressed in a variety of human cancers, including colon, esophageal, and hepatocellular carcinomas relative to the corresponding normal tissues (5).…”

Section: Introductionmentioning

confidence: 99%

Cancer Cell Dependence on Unsaturated Fatty Acids Implicates Stearoyl-CoA Desaturase as a Target for Cancer Therapy

Roongta

Pabalan

Wang

et al. 2011

Molecular Cancer Research

234

199

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Emerging literature suggests that metabolic pathways play an important role in the maintenance and progression of human cancers. In particular, recent studies have implicated lipid biosynthesis and desaturation as a requirement for tumor cell survival. In the studies reported here, we aimed to understand whether tumor cells require the activity of either human isoform of stearoyl-CoA-desaturase (SCD1 or SCD5) for survival. Inhibition of SCD1 by siRNA or a small molecule antagonist results in strong induction of apoptosis and growth inhibition, when tumor cells are cultured in reduced (2%) serum conditions, but has little impact on cells cultured in 10% serum. Depletion of SCD5 had minimal effects on cell growth or apoptosis. Consistent with the observed dependence on SCD1, but not SCD5, levels of SCD1 protein increased in response to decreasing serum levels. Both induction of SCD1 protein and sensitivity to growth inhibition by SCD1 inhibition could be reversed by supplementing growth media with unsaturated fatty acids, the product of the enzymatic reaction catalyzed by SCD1. Transcription profiling of cells treated with an SCD inhibitor revealed strong induction of markers of endoplasmic reticulum stress. Underscoring its importance in cancer, SCD1 protein was found to be highly expressed in a large percentage of human cancer specimens. SCD inhibition resulted in tumor growth delay in a human gastric cancer xenograft model. Altogether, these results suggest that desaturated fatty acids are required for tumor cell survival and that SCD may represent a viable target for the development of novel agents for cancer therapy. Mol Cancer Res; 9(11); 1551-61. Ó2011 AACR.

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Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer

Cited by 273 publications

References 84 publications

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1

Difference in fatty acids composition of breast adipose tissue in women with breast cancer and benign breast disease

Cancer Cell Dependence on Unsaturated Fatty Acids Implicates Stearoyl-CoA Desaturase as a Target for Cancer Therapy

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