title: Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and activated by amplification in squamous cell carcinomas.
abstract: 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.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Inderpal
authors.initials: I
authors.lastname: Sarkaria
authors.forename: Pornchai
authors.initials: P
authors.lastname: O-charoenrat
authors.forename: Simon G
authors.initials: SG
authors.lastname: Talbot
authors.forename: Pabbathi G
authors.initials: PG
authors.lastname: Reddy
authors.forename: Ivan
authors.initials: I
authors.lastname: Ngai
authors.forename: Ellie
authors.initials: E
authors.lastname: Maghami
authors.forename: Kepal N
authors.initials: KN
authors.lastname: Patel
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lee
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: Maria
authors.initials: M
authors.lastname: Dudas
authors.forename: Andrew
authors.initials: A
authors.lastname: Kaufman
authors.forename: Russell
authors.initials: R
authors.lastname: Ryan
authors.forename: Ronald
authors.initials: R
authors.lastname: Ghossein
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.forename: Archontoula
authors.initials: A
authors.lastname: Stoffel
authors.forename: Y
authors.initials: Y
authors.lastname: Ramanathan
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: 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
chemical_list: 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