Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and activated by amplification in squamous cell carcinomas.
Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage.
Sarkaria
Inderpal
I
Laboratory of Epithelial Cancer Biology, Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
O-charoenrat
Pornchai
P
Talbot
Simon G
SG
Reddy
Pabbathi G
PG
Ngai
Ivan
I
Maghami
Ellie
E
Patel
Kepal N
KN
Lee
Benjamin
B
Yonekawa
Yoshihiro
Y
Dudas
Maria
M
Kaufman
Andrew
A
Ryan
Russell
R
Ghossein
Ronald
R
Rao
Pulivarthi H
PH
Stoffel
Archontoula
A
Ramanathan
Y
Y
Singh
Bhuvanesh
B
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003001:Cloning, Molecular; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells / Q000473:pathology / Q000637:transplantation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D011506:Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D000071676:Zinc Finger Protein GLI1
C408631:DCUN1D1 protein, human; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1