TY - JOUR
T1 - A Virus Causes Cancer by Inducing Massive Chromosomal Instability through Cell Fusion
AU - Duelli, Dominik M.
AU - Padilla-Nash, Hesed M.
AU - Berman, David
AU - Murphy, Kathleen M.
AU - Ried, Thomas
AU - Lazebnik, Yuri
PY - 2007/3/6
Y1 - 2007/3/6
N2 - Chromosomal instability (CIN) underlies malignant properties of many solid cancers and their ability to escape therapy, and it might itself cause cancer [1, 2]. CIN is sustained by deficiencies in proteins, such as the tumor suppressor p53 [3-5], that police genome integrity, but the primary cause of CIN in sporadic cancers remains uncertain [6, 7]. The primary suspects are mutations that deregulate telomere maintenance, or mitosis, yet such mutations have not been identified in the majority of sporadic cancers [6]. Alternatively, CIN could be caused by a transient event that destabilizes the genome without permanently affecting mechanisms of mitosis or proliferation [5, 8]. Here, we show that an otherwise harmless virus rapidly causes massive chromosomal instability by fusing cells whose cell cycle is deregulated by oncogenes. This synergy between fusion and oncogenes "randomizes" normal diploid human fibroblasts so extensively that each analyzed cell has a unique karyotype, and some produce aggressive, highly aneuploid, heterogeneous, and transplantable epithelial cancers in mice. Because many viruses are fusogenic, this study suggests that viruses, including those that have not been linked to carcinogenesis, can cause chromosomal instability and, consequently, cancer by fusing cells.
AB - Chromosomal instability (CIN) underlies malignant properties of many solid cancers and their ability to escape therapy, and it might itself cause cancer [1, 2]. CIN is sustained by deficiencies in proteins, such as the tumor suppressor p53 [3-5], that police genome integrity, but the primary cause of CIN in sporadic cancers remains uncertain [6, 7]. The primary suspects are mutations that deregulate telomere maintenance, or mitosis, yet such mutations have not been identified in the majority of sporadic cancers [6]. Alternatively, CIN could be caused by a transient event that destabilizes the genome without permanently affecting mechanisms of mitosis or proliferation [5, 8]. Here, we show that an otherwise harmless virus rapidly causes massive chromosomal instability by fusing cells whose cell cycle is deregulated by oncogenes. This synergy between fusion and oncogenes "randomizes" normal diploid human fibroblasts so extensively that each analyzed cell has a unique karyotype, and some produce aggressive, highly aneuploid, heterogeneous, and transplantable epithelial cancers in mice. Because many viruses are fusogenic, this study suggests that viruses, including those that have not been linked to carcinogenesis, can cause chromosomal instability and, consequently, cancer by fusing cells.
KW - CELLCYCLE
KW - DNA
KW - MICROBIO
UR - http://www.scopus.com/inward/record.url?scp=33847391958&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847391958&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2007.01.049
DO - 10.1016/j.cub.2007.01.049
M3 - Article
C2 - 17320392
AN - SCOPUS:33847391958
SN - 0960-9822
VL - 17
SP - 431
EP - 437
JO - Current Biology
JF - Current Biology
IS - 5
ER -