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TGF-beta-mediated epithelial-mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma

Miyashita, Naoya (author)
Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
Enokido, Takayoshi (author)
Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
Horie, Masafumi (author)
Osaka Univ, Grad Sch Med, Dept Canc Genome Informat, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.,University of Tokyo
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Fukuda, Kensuke (author)
Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
Urushiyama, Hirokazu (author)
Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
Strell, Carina (author)
Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
Brunnström, Hans (author)
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
Micke, Patrick (author)
Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
Saito, Akira (author)
Univ Tokyo, Grad Sch Med, Dept Resp Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.,University of Tokyo
Nagase, Takahide (author)
Univ Tokyo, Grad Sch Med, Dept Resp Med, 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)
2021-11-17
2021
English.
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
Related links:
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http://dx.doi.org/10... (free)
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal phenotypes. Cancer cells undergo EMT to acquire malignant features and TGF-beta is a key regulator of EMT. Here, we demonstrate for the first time that TGF-beta could elicit EMT in a mouse lung adenocarcinoma cell line. TGF-beta signaling activation led to cell morphological changes corresponding to EMT and enhanced the expression of mesenchymal markers and EMT-associated transcription factors in CMT64 lung cancer cells. RNA-sequencing analyses revealed that TGF-beta increases expression of Tead transcription factors and an array of Tead2 target genes. TGF-beta stimulation also resulted in alternative splicing of several genes including Cd44, tight junction protein 1 (Tjp1), and Cortactin (Cttn). In parallel with EMT, TGF-beta enhanced cell growth of CMT64 cells and promoted tumor formation in a syngeneic transplantation model. Of clinical importance, the expression of TGF-beta-induced genes identified in CMT64 cells correlated with EMT gene signatures in human lung adenocarcinoma tissue samples. Furthermore, TGF-beta-induced gene enrichment was related to poor prognosis, underscoring the tumor-promoting role of TGF-beta signaling in lung adenocarcinoma. Our cellular and syngeneic transplantation model would provide a simple and useful experimental tool to study the significance of TGF-beta signaling and EMT.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Pathology
Patologi

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