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Article Basal cell ...
Article Basal cell carcinomas acquire secondary mutations to overcome dormancy and progress from microscopic to macroscopic disease
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- Trieu, Kenneth G. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Tsai, Shih-Ying (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Eberl, Markus (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Ju, Virginia (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Ford, Noah C. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Doane, Owen J. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Peterson, Jamie K. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Veniaminova, Natalia A. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Grachtchouk, Marina (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Harms, Paul W. (author)
- Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA.
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- Swartling, Fredrik J., 1975- (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Dlugosz, Andrzej A. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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- Wong, Sunny Y. (author)
- Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
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Univ Michigan, Dept Dermatol, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. (creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
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In: Cell Reports. - : Elsevier. - 2211-1247. ; 39:5
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Abstract
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- Basal cell carcinomas (BCCs) frequently possess immense mutational burdens; however, the functional significance of most of these mutations remains unclear. Here, we report that loss of Ptch1, the most common mutation that activates upstream Hedgehog (Hh) signaling, initiates the formation of nascent BCC-like tumors that eventually enter into a dormant state. However, rare tumors that overcome dormancy acquire the ability to hyperactivate downstream Hh signaling through a variety of mechanisms, including amplification of Gli1/2 and upregulation of Mycn. Furthermore, we demonstrate that MYCN overexpression promotes the progression of tumors induced by loss of Ptch1. These findings suggest that canonical mutations that activate upstream Hh signaling are necessary, but not sufficient, for BCC to fully progress. Rather, tumors likely acquire secondary mutations that further hyperactivate downstream Hh signaling in order to escape dormancy and enter a trajectory of uncontrolled expansion.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Trieu, Kenneth G ...
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Tsai, Shih-Ying
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Eberl, Markus
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Ju, Virginia
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Ford, Noah C.
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Doane, Owen J.
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show more...
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Peterson, Jamie ...
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Veniaminova, Nat ...
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Grachtchouk, Mar ...
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Harms, Paul W.
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Swartling, Fredr ...
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Dlugosz, Andrzej ...
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Wong, Sunny Y.
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell Reports
- By the university
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Uppsala University