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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)527-538
Number of pages12
JournalCell Reports
Volume7
Issue number2
DOIs
Publication statusPublished - 2014 Apr 24

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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