TY - JOUR
T1 - TSPAN2 Is Involved in Cell Invasion and Motility during Lung Cancer Progression
AU - Otsubo, Chihiro
AU - Otomo, Ryo
AU - Miyazaki, Makoto
AU - Matsushima-Hibiya, Yuko
AU - Kohno, Takashi
AU - Iwakawa, Reika
AU - Takeshita, Fumitaka
AU - Okayama, Hirokazu
AU - Ichikawa, Hitoshi
AU - Saya, Hideyuki
AU - Kiyono, Tohru
AU - Ochiya, Takahiro
AU - Tashiro, Fumio
AU - Nakagama, Hitoshi
AU - Yokota, Jun
AU - Enari, Masato
N1 - Funding Information:
We are grateful to Dr. Teruhiko Yoshida (National Cancer Center Research Institute, Japan) and Ms. Sachiyo Mimaki (National Cancer Center Research Institute, Japan) for expression profiling. This work was supported in part by Grants-in-Aid from Ministry of Education, Culture, Sports, Science and Technology (MEXT) for Scientific Research on Priority Areas (17013088) and for Scientific Research (B) (21370083) from the Ministry of Health, Labour and Welfare (MHLW) for the third-term Comprehensive 10-year Strategy for Cancer Control (CSCC), the National Cancer Center (NCC) Research and Development Fund (M.E., 23-B-27[23-A-37]; Core Facility, 23-A-7), and a Grant-in-Aid for JSPS Fellows (10J02622) (C.O.).
PY - 2014/4/24
Y1 - 2014/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899627865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899627865&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2014.03.027
DO - 10.1016/j.celrep.2014.03.027
M3 - Article
C2 - 24726368
AN - SCOPUS:84899627865
SN - 2211-1247
VL - 7
SP - 527
EP - 538
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -
