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タイトル: The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.
著者: Itou, Junji  kyouindb  KAKEN_id
Tanaka, Sunao
Li, Wenzhao
Iida, Atsuo
Sehara-Fujisawa, Atsuko
Sato, Fumiaki
Toi, Masakazu
著者名の別形: 伊東, 潤二
田中, 直
李, 文昭
飯田, 敦夫
瀬原, 淳子
佐藤, 史顕
戸井, 雅和
キーワード: Breast cancer
Cell migration
Focal adhesion dynamics
Integrin
SALL4
発行日: Jan-2017
出版者: Elsevier B.V.
誌名: Biochimica et biophysica acta
巻: 1864
号: 1
開始ページ: 76
終了ページ: 88
抄録: During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1. In addition, we clarified that integrin α6 and β1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6β1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6β1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6β1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration.
記述: 乳がん細胞の転移を促進する新たなメカニズムの解明 --SALL4 - integrin α6β1系による移動能力の亢進--. 京都大学プレスリリース. 2016-11-08.
著作権等: © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
The full-text file will be made open to the public on 01 January 2018 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/217245
DOI(出版社版): 10.1016/j.bbamcr.2016.10.012
PubMed ID: 27773610
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2016/161020_2.html
出現コレクション:学術雑誌掲載論文等

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