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Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness

Recent studies have revealed that dysregulated Rab small GTPase-mediated vesicle trafficking pathways are associated with cancer progression. However, whether any of the Rabs plays a suppressor role in cancer stemness is least explored. Rab37 has been postulated as a tumor suppressive small GTPase f...

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Autores principales: Cho, Shu-Huei, Kuo, I-Ying, Lu, Pei-Jung Frank, Tzeng, Hong-Tai, Lai, Wu-Wei, Su, Wu-Chou, Wang, Yi-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115395/
https://www.ncbi.nlm.nih.gov/pubmed/30158579
http://dx.doi.org/10.1038/s41419-018-0915-0
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author Cho, Shu-Huei
Kuo, I-Ying
Lu, Pei-Jung Frank
Tzeng, Hong-Tai
Lai, Wu-Wei
Su, Wu-Chou
Wang, Yi-Ching
author_facet Cho, Shu-Huei
Kuo, I-Ying
Lu, Pei-Jung Frank
Tzeng, Hong-Tai
Lai, Wu-Wei
Su, Wu-Chou
Wang, Yi-Ching
author_sort Cho, Shu-Huei
collection PubMed
description Recent studies have revealed that dysregulated Rab small GTPase-mediated vesicle trafficking pathways are associated with cancer progression. However, whether any of the Rabs plays a suppressor role in cancer stemness is least explored. Rab37 has been postulated as a tumor suppressive small GTPase for trafficking anti-tumor cargos. Here, we report a previously uncharacterized mechanism by which Rab37 mediates exocytosis of secreted frizzled-related protein-1 (SFRP1), an extracellular antagonist of Wnt, to suppress Wnt signaling and cancer stemness in vitro and in vivo. Reconstitution experiments indicate that SFRP1 secretion is crucial for Rab37-mediated cancer stemness suppression and treatment with SRPP1 recombinant protein reduces xenograft tumor initiation ability. Clinical results confirm that concordantly low Rab37, low SFRP1, and high Oct4 stemness protein expression profile can be used as a biomarker to predict poor prognosis in lung cancer patients. Our findings reveal that Rab37-mediated SFRP1 secretion suppresses cancer stemness, and dysregulated Rab37-SFRP1 pathway confers cancer stemness via the activation of Wnt signaling. Rab37-SFRP1-Wnt axis could be a potential therapeutic target for attenuating lung cancer stemness.
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spelling pubmed-61153952018-08-30 Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness Cho, Shu-Huei Kuo, I-Ying Lu, Pei-Jung Frank Tzeng, Hong-Tai Lai, Wu-Wei Su, Wu-Chou Wang, Yi-Ching Cell Death Dis Article Recent studies have revealed that dysregulated Rab small GTPase-mediated vesicle trafficking pathways are associated with cancer progression. However, whether any of the Rabs plays a suppressor role in cancer stemness is least explored. Rab37 has been postulated as a tumor suppressive small GTPase for trafficking anti-tumor cargos. Here, we report a previously uncharacterized mechanism by which Rab37 mediates exocytosis of secreted frizzled-related protein-1 (SFRP1), an extracellular antagonist of Wnt, to suppress Wnt signaling and cancer stemness in vitro and in vivo. Reconstitution experiments indicate that SFRP1 secretion is crucial for Rab37-mediated cancer stemness suppression and treatment with SRPP1 recombinant protein reduces xenograft tumor initiation ability. Clinical results confirm that concordantly low Rab37, low SFRP1, and high Oct4 stemness protein expression profile can be used as a biomarker to predict poor prognosis in lung cancer patients. Our findings reveal that Rab37-mediated SFRP1 secretion suppresses cancer stemness, and dysregulated Rab37-SFRP1 pathway confers cancer stemness via the activation of Wnt signaling. Rab37-SFRP1-Wnt axis could be a potential therapeutic target for attenuating lung cancer stemness. Nature Publishing Group UK 2018-08-29 /pmc/articles/PMC6115395/ /pubmed/30158579 http://dx.doi.org/10.1038/s41419-018-0915-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cho, Shu-Huei
Kuo, I-Ying
Lu, Pei-Jung Frank
Tzeng, Hong-Tai
Lai, Wu-Wei
Su, Wu-Chou
Wang, Yi-Ching
Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness
title Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness
title_full Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness
title_fullStr Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness
title_full_unstemmed Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness
title_short Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness
title_sort rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit wnt signaling and thus suppress lung cancer stemness
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115395/
https://www.ncbi.nlm.nih.gov/pubmed/30158579
http://dx.doi.org/10.1038/s41419-018-0915-0
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