SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.
Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.
Bass
Adam J
AJ
Watanabe
Hideo
H
Mermel
Craig H
CH
Yu
Soyoung
S
Perner
Sven
S
Verhaak
Roel G
RG
Kim
So Young
SY
Wardwell
Leslie
L
Tamayo
Pablo
P
Gat-Viks
Irit
I
Ramos
Alex H
AH
Woo
Michele S
MS
Weir
Barbara A
BA
Getz
Gad
G
Beroukhim
Rameen
R
O'Kelly
Michael
M
Dutt
Amit
A
Rozenblatt-Rosen
Orit
O
Dziunycz
Piotr
P
Komisarof
Justin
J
Chirieac
Lucian R
LR
Lafargue
Christopher J
CJ
Scheble
Veit
V
Wilbertz
Theresia
T
Ma
Changqing
C
Rao
Shilpa
S
Nakagawa
Hiroshi
H
Stairs
Douglas B
DB
Lin
Lin
L
Giordano
Thomas J
TJ
Wagner
Patrick
P
Minna
John D
JD
Gazdar
Adi F
AF
Zhu
Chang Qi
CQ
Brose
Marcia S
MS
Cecconello
Ivan
I
Ribeiro
Ulysses
U
Marie
Suely K
SK
Dahl
Olav
O
Shivdasani
Ramesh A
RA
Tsao
Ming-Sound
MS
Rubin
Mark A
MA
Wong
Kwok K
KK
Regev
Aviv
A
Hahn
William C
WC
Beer
David G
DG
Rustgi
Anil K
AK
Meyerson
Matthew
M
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005784:Gene Amplification; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009857:Oncogenes / Q000235:genetics*; D034622:RNA Interference; D055748:SOXB1 Transcription Factors / Q000235:genetics*
C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors