Targeting metastasis-initiating cells through the fatty acid receptor CD36

Pascual, Gloria; Avgustinova, Alexandra; Mejetta, Stefania; Martı́n, Mercé; Castellanos, Andrés; Attolini, Camille Stephan‐Otto; Berenguer, Antoni; Prats, Neus; Toll, Agustí; Hueto, Juan Antonio; Bescós‐Atín, Coro; Croce, Luciano Di; Benitah, Salvador Aznar

doi:10.1038/nature20791

Cited by 1,105 publications

(1,116 citation statements)

References 67 publications

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“…A subpopulation of cancer cells with high CD36 expression has unique metastasis-initiating potential, highlighting a key role of CD36-regulated lipid metabolism and signaling in metastatic colonization (45). Lysophosphatidic acid/protein kinase D1/CD36 signaling is a bona fide breast cancer promoter via stimulating microvascular remodeling in chronic diet-induced obesity (46).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes

Sun

Tan

Huang

et al. 2018

Journal of Biological Chemistry

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Both the magnitude and duration of insulin signaling are important in executing its cellular functions. Insulin-induced degradation of insulin receptor substrate 1 (IRS1) represents a key negative feedback loop that restricts insulin signaling. Moreover, high concentrations of fatty acids (FAs) and glucose involved in the etiology of obesity-associated insulin resistance also contribute to the regulation of IRS1 degradation. The scavenger receptor CD36 binds many lipid ligands and its contribution to insulin resistance has been extensively studied, but the exact regulation of insulin sensitivity by CD36 is highly controversial. Herein, we found that CD36 knockdown in C2C12 myotubes accelerated insulin-stimulated Akt activation, but the activated signaling was sustained for a much shorter period of time as compared to wild type cells, leading to exacerbated insulin-induced insulin resistance. This was likely due to enhanced insulin-induced IRS1 degradation after CD36 knockdown. Overexpression of wild type CD36, but not a ubiquitination-defective CD36 mutant delayed Akt activation. We also found that CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with cullin 7, a key component of the multi-subunit cullin-RING E3 ubiquitin ligase complex. Moreover, dissociation of the Src family kinase Fyn from CD36 by free FAs or Fyn knockdown/inhibition accelerated insulin-induced IRS1 degradation, likely due to disrupted IRS1 interaction with CD36 and thus enhanced binding to cullin 7. In summary, we identified a CD36-dependent FA-sensing pathway that plays an important role in negative feedback regulation of insulin activation and may open up strategies for preventing or managing type 2 diabetes mellitus.Cell signaling is usually initiated by binding an activating ligand to a receptor on the plasma membrane (PM) that transmits the signal inside the cell. Distinct cellular responses and outcomes of a signaling pathway are achieved by precise regulation of its duration, magnitude and subcellular compartmentalization, which is mediated by an integrated network with multiple http://www.jbc.org/cgi

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Section: Discussionmentioning

confidence: 99%

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes

Sun

Tan

Huang

et al. 2018

Journal of Biological Chemistry

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“…Growing evidence indicates that the Warburg effect may contribute to the early stages of cancer progression. Instead, the reprogramming of fatty acid (FA) metabolism in cancer cells may provide a selective advantage toward the metastatic process [8,9]. FAs are the major building blocks for energy metabolism and represent the essential components of the signal transduction network of biological membranes.…”

Section: Introductionmentioning

confidence: 99%

LNMICC Promotes Nodal Metastasis of Cervical Cancer by Reprogramming Fatty Acid Metabolism

et al. 2018

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Running Title: LNMICC promotes lymph node metastasis in cervical cancer.Key words: lymph node metastasis; fatty acid metabolism; long non-coding RNA; cervical cancer. Conflict of Interest:The authors declare no potential conflicts of interest.Research. AbstractCancer spread to lymph nodes (LN) predicts poor survival but underlying mechanisms remain little understood. In this study, we show that overexpression of the long non-coding RNA LNMICC associates with LN metastasis of primary cervical cancer, where it serves as an independent high-risk factor in patient survival. Functional investigations demonstrated that LNMICC promoted LN metastasis by reprogramming fatty acid metabolism, by recruiting the nuclear factor NPM1 to the promoter of the fatty acid binding protein FABP5. We also found that the pro-metastatic effects of LNMICC were directly targeted and suppressed by miR-190. Our results establish a new mechanism of LN metastasis and highlight LNMICC as a candidate prognostic biomarker and therapeutic target in cervical cancer.

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“…In this work, we have studied the eff ect of titanium nitride and chromium disilicide nanoparticles on the expression of a subset of genes encoding different regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, CD36, and PECAM1) and enzyme SNARK/NUAK2, which play an important role in various metabolic pathways and thus control the cell proliferation and apoptosis as well as angiogenesis and metastasis (Praveen Kumar et al 2014;Baxter 2015;Kim and Lee 2015;Musumeci et al 2015;Ding et al 2016;Kim et al 2016;Miller et al 2016;Phillips et al 2016;Guaita-Esteruelas et al 2017;Pascual et al 2017). For titanium dioxide nanoparticles, which are widely used in the number of applications, including cosmetic creams, toothpastes, and component of surgical implants, it has been shown that long-term exposure to these nanoparticles led to accumulation of these nanoparticles in brain, over-proliferation of glial cells and signifi cant changes in brain gene expressions as well as to neurogenic disease states in mice (Ze et al 2014;Rollerova et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that proteins encoded by all these genes play an important role in controlling of cell proliferation, apoptosis, cancer growth, and angiogenesis (Praveen Kumar et al 2014;Bach 2015;Baxter 2015;GuaitaEsteruelas et al 2017;Pascual et al 2017). Moreover, CD36 antigen may also play a role in the pathogenesis of impaired fasting glucose/impaired glucose tolerance and type 2 diabetes (Wang et al 2012).…”

Section: Igfbp3 Igfbp4mentioning

confidence: 99%

“…Furthermore, miR-143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma because this miRNA as well as miR-1 directly regulate NUAK2 oncogene (Fu et al 2016;Miller et al 2016). CD36 (cluster determinant 36), also known as leukocyte diff erentiation antigen CD36, thrombospondin receptor, collagen type I receptor, and FAT (fatty acid translocase), seems to have numerous potential physiological functions (Pascual et al 2017). CD36 functions as a cell adhesion molecule and its inhibition impairs metastasis.…”

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confidence: 99%

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Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

Minchenko

Tsymbal

Yavorovsky

et al. 2017

Endocrine Regulations

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Objective. Th e aim of the present study was to examine the eff ect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic eff ects of these nanoparticles.Methods. Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. Th e expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction.Results. Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was signifi cantly stronger as compared to titanium nitride nanoparticles.Conclusions. Th e results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable eff ects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may refl ect the genotoxic activities of the studied nanoparticles. A rapid development of nanoscience and nanotechnologies has given a rise to the wide range of applications of man-made nanomaterials in specifi c biomedical fi elds for treatment, diagnosing, controlling, and repairing of biological systems at the molecular level. Titanium nitride nanoparticles have favorable properties and are used for the coating of orthopedic implants, coronary stents, and syringe needles as well as for improving long-term implants in the dental medicine. However, very little is known Unauthenticated Download Date | 5/12/18 12:12 PM

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Targeting metastasis-initiating cells through the fatty acid receptor CD36

Cited by 1,105 publications

References 67 publications

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes

LNMICC Promotes Nodal Metastasis of Cervical Cancer by Reprogramming Fatty Acid Metabolism

Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

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