TSPAN2 Is Involved in Cell Invasion and Motility during Lung Cancer Progression

Chihiro Otsubo, Ryo Otomo, Makoto Miyazaki, Yuko Matsushima-Hibiya, Takashi Kohno, Reika Iwakawa, Fumitaka Takeshita, Hirokazu Okayama, Hitoshi Ichikawa, Hideyuki Saya, Tohru Kiyono, Takahiro Ochiya, Fumio Tashiro, Hitoshi Nakagama, Jun Yokota, Masato Enari

研究成果: Article

19 引用 (Scopus)

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In lung cancer progression, p53 mutations are more often observed in invasive tumors than in noninvasive tumors, suggesting that p53 is involved in tumor invasion and metastasis. To understand the nature of p53 function as a tumor suppressor, it is crucial to elucidate the detailed mechanism of the alteration in epithelial cells that follow oncogenic KRAS activation and p53 inactivation. Here, we report that KRAS activation induces epithelial-mesenchymal transitionand that p53 inactivation is required for cell motility and invasiveness. Furthermore, TSPAN2, atransmembrane protein, is responsible for cell motility and invasiveness elicited by p53 inactivation. TSPAN2 is highly expressed in p53-mutated lung cancer cells, and high expression of TSPAN2 is associated with the poor prognosis of lung adenocarinomas. TSPAN2 knockdown suppresses metastasis tothe lungs and liver, enabling prolonged survival. TSPAN2 enhances cell motility and invasiveness by assisting CD44 in scavenging intracellular reactive oxygen species.

元の言語English
ページ(範囲)527-538
ページ数12
ジャーナルCell Reports
7
発行部数2
DOI
出版物ステータスPublished - 2014 4 24

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Otsubo, C., Otomo, R., Miyazaki, M., Matsushima-Hibiya, Y., Kohno, T., Iwakawa, R., Takeshita, F., Okayama, H., Ichikawa, H., Saya, H., Kiyono, T., Ochiya, T., Tashiro, F., Nakagama, H., Yokota, J., & Enari, M. (2014). TSPAN2 Is Involved in Cell Invasion and Motility during Lung Cancer Progression. Cell Reports, 7(2), 527-538. https://doi.org/10.1016/j.celrep.2014.03.027