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Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development

(2010) CANCER RESEARCH. 70(22). p.9453-9462
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Abstract
Aberrant activation of fatty acid synthesis is a key feature of many advanced human cancers. Unlike in classical lipogenic tissues, this process has been implicated in membrane production required for rapid cell proliferation. Here, to gain further insight into the consequences of tumor-associated fatty acid synthesis, we have mimicked the lipogenic phenotype of cancer cells in Xenopus embryos by microinjection of RNA encoding the lipogenic transcription factor sterol regulatory element binding protein 1c (SREBP1c). Dramatic morphologic changes were observed that could be linked to alterations in Wnt and Hedgehog signaling, and ultimately to a distortion of the primary cilium. This is a sophisticated microtubular sensory organelle that is expressed on the surface of nearly every cell type and that is lost in many cancers. SREBP1c-induced loss of the primary cilium could be confirmed in mammalian Madin-Darby canine kidney (MDCK) cells and was mediated by changes in the supply of fatty acids. Conversely, inhibition of fatty acid synthesis in highly lipogenic human prostate cancer cells restored the formation of the primary cilium. Lipid-induced ciliary loss was associated with mislocalization of apical proteins, distortion of cell polarization, and aberrant epithelial tissue development as revealed in three-dimensional cultures of MDCK cells and in the developing mouse prostate. These data imply that tumor-associated lipogenesis, in addition to rendering cells more autonomous in terms of lipid supply, disturbs cilium formation and contributes to impaired environmental sensing, aberrant signaling, and distortion of polarized tissue architecture, which are all hallmarks of cancer.
Keywords
ACETYL-COA CARBOXYLASE, PLANAR CELL POLARITY, PROSTATE-CANCER, BETA-CATENIN, SYNTHASE, GROWTH, CILIOGENESIS, EXPRESSION, PROTEINS, XENOPUS

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Chicago
Willemarck, Nicolas, Evelien Rysman, Koen Brusselmans, Griet Van Imschoot, Frank Vanderhoydonc, Katrien Moerloose, Evelyne Lerut, et al. 2010. “Aberrant Activation of Fatty Acid Synthesis Suppresses Primary Cilium Formation and Distorts Tissue Development.” Cancer Research 70 (22): 9453–9462.
APA
Willemarck, N., Rysman, E., Brusselmans, K., Van Imschoot, G., Vanderhoydonc, F., Moerloose, K., Lerut, E., et al. (2010). Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development. CANCER RESEARCH, 70(22), 9453–9462.
Vancouver
1.
Willemarck N, Rysman E, Brusselmans K, Van Imschoot G, Vanderhoydonc F, Moerloose K, et al. Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development. CANCER RESEARCH. 2010;70(22):9453–62.
MLA
Willemarck, Nicolas, Evelien Rysman, Koen Brusselmans, et al. “Aberrant Activation of Fatty Acid Synthesis Suppresses Primary Cilium Formation and Distorts Tissue Development.” CANCER RESEARCH 70.22 (2010): 9453–9462. Print.
@article{1082124,
  abstract     = {Aberrant activation of fatty acid synthesis is a key feature of many advanced human cancers. Unlike in classical lipogenic tissues, this process has been implicated in membrane production required for rapid cell proliferation. Here, to gain further insight into the consequences of tumor-associated fatty acid synthesis, we have mimicked the lipogenic phenotype of cancer cells in Xenopus embryos by microinjection of RNA encoding the lipogenic transcription factor sterol regulatory element binding protein 1c (SREBP1c). Dramatic morphologic changes were observed that could be linked to alterations in Wnt and Hedgehog signaling, and ultimately to a distortion of the primary cilium. This is a sophisticated microtubular sensory organelle that is expressed on the surface of nearly every cell type and that is lost in many cancers. SREBP1c-induced loss of the primary cilium could be confirmed in mammalian Madin-Darby canine kidney (MDCK) cells and was mediated by changes in the supply of fatty acids. Conversely, inhibition of fatty acid synthesis in highly lipogenic human prostate cancer cells restored the formation of the primary cilium. Lipid-induced ciliary loss was associated with mislocalization of apical proteins, distortion of cell polarization, and aberrant epithelial tissue development as revealed in three-dimensional cultures of MDCK cells and in the developing mouse prostate. These data imply that tumor-associated lipogenesis, in addition to rendering cells more autonomous in terms of lipid supply, disturbs cilium formation and contributes to impaired environmental sensing, aberrant signaling, and distortion of polarized tissue architecture, which are all hallmarks of cancer.},
  author       = {Willemarck, Nicolas and Rysman, Evelien and Brusselmans, Koen and Van Imschoot, Griet and Vanderhoydonc, Frank and Moerloose, Katrien and Lerut, Evelyne and Verhoeven, Guido and Van Roy, Frans and Vleminckx, Kris and Swinnen, Johannes V},
  issn         = {0008-5472},
  journal      = {CANCER RESEARCH},
  keywords     = {ACETYL-COA CARBOXYLASE,PLANAR CELL POLARITY,PROSTATE-CANCER,BETA-CATENIN,SYNTHASE,GROWTH,CILIOGENESIS,EXPRESSION,PROTEINS,XENOPUS},
  language     = {eng},
  number       = {22},
  pages        = {9453--9462},
  title        = {Aberrant activation of fatty acid synthesis suppresses primary cilium formation and distorts tissue development},
  url          = {http://dx.doi.org/10.1158/0008-5472.CAN-10-2324},
  volume       = {70},
  year         = {2010},
}

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