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ASCL1 promotes tumo...
ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma
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- Miyashita, Naoya (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Horie, Masafumi (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;Osaka Univ, Grad Sch Med, Dept Canc Genome Informat, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.,University of Tokyo,Osaka University
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- Mikami, Yu (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;Univ North Carolina Chapel Hill, Marsico Lung Inst, Cyst Fibrosis Res Ctr, Chapel Hill, NC USA.,University of North Carolina,University of Tokyo
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- Urushiyama, Hirokazu (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Fukuda, Kensuke (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Miyakawa, Kazuko (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Matsuzaki, Hirotaka (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Makita, Kosuke (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;McGill Univ, Meakins Christie Labs, Res Inst, Hlth Ctr, Montreal, PQ, Canada.,McGill University Health Center,University of Tokyo
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- Morishita, Yasuyuki (författare)
- Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Harada, Hiroaki (författare)
- Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Backman, Max (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Lindskog, Cecilia (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi
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- Brunnström, Hans (författare)
- Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Micke, Patrick (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Nagase, Takahide (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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- Saito, Akira (författare)
- Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;Univ Tokyo, Div Hlth Serv Promot, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
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Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan University of Tokyo (creator_code:org_t)
- Elsevier BV, 2020
- 2020
- Engelska.
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 489, s. 121-132
- Relaterad länk:
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- The master regulator of neuroendocrine differentiation, achaete-scute complex homolog 1 (ASCL1) defines a subgroup of lung adenocarcinoma. However, the mechanistic role of ASCL1 in lung tumorigenesis and its relation to the immune microenvironment is principally unknown. Here, the immune landscape of ASCL1-positive lung adenocarcinomas was characterized by immunohistochemistry. Furthermore, ASCL1 was transduced in mouse lung adenocarcinoma cell lines and comparative RNA-sequencing and secretome analyses were performed. The effects of ASCL1 on tumorigenesis were explored in an orthotopic syngeneic transplantation model.ASCL1-positive lung adenocarcinomas revealed lower infiltration of CD8+, CD4+, CD20+, and FOXP3+ lymphocytes and CD163+ macrophages indicating an immune desert phenotype. Ectopic ASCL1 upregulated cyclin transcript levels, stimulated cell proliferation, and enhanced tumor growth in mice. ASCL1 suppressed secretion of chemokines, including CCL20, CXCL2, CXCL10, and CXCL16, indicating effects on immune cell trafficking. In accordance with lower lymphocytes infiltration, ASCL1-positive lung adenocarcinomas demonstrated lower abundance of CXCR3-and CCR6-expressing cells.In conclusion, ASCL1 mediates its tumor-promoting effect not only through cell-autonomous signaling but also by modulating chemokine production and immune responses. These findings suggest that ASCL1-positive tumors represent a clinically relevant lung cancer entity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Nyckelord
- Lungadenocarcinoma
- ASCL1
- Chemokine
- Neuroendocrine
- Immunotherapy
- Patologi
- Pathology
- ASCL1
- Chemokine
- Immunotherapy
- Lung adenocarcinoma
- Neuroendocrine
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Miyashita, Naoya
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Horie, Masafumi
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Mikami, Yu
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Urushiyama, Hiro ...
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Fukuda, Kensuke
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Miyakawa, Kazuko
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visa fler...
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Matsuzaki, Hirot ...
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Makita, Kosuke
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Morishita, Yasuy ...
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Harada, Hiroaki
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Backman, Max
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Lindskog, Cecili ...
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Brunnström, Hans
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Micke, Patrick
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Nagase, Takahide
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Saito, Akira
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Klinisk laborato ...
- Artiklar i publikationen
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Cancer Letters
- Av lärosätet
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Uppsala universitet
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Lunds universitet