title: The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma.
abstract: We report that two oncogenes coamplified on chromosome 3q26, PRKCI and SOX2, cooperate to drive a stem-like phenotype in lung squamous cell carcinoma (LSCC). Protein kinase Cι (PKCι) phosphorylates SOX2, a master transcriptional regulator of stemness, and recruits it to the promoter of Hedgehog (Hh) acyltransferase (HHAT) that catalyzes the rate-limiting step in Hh ligand production. PKCι-mediated SOX2 phosphorylation is required for HHAT promoter occupancy, HHAT expression, and maintenance of a stem-like phenotype. Primary LSCC tumors coordinately overexpress PKCι, SOX2, and HHAT and require PKCι-SOX2-HHAT signaling to maintain a stem-like phenotype. Thus, PKCι and SOX2 are genetically, biochemically, and functionally linked in LSCC, and together they drive tumorigenesis by establishing a cell-autonomous Hh signaling axis.
authors: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors: Verline
authors: V
authors: Justilien
authors: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors: Michael P
authors: MP
authors: Walsh
authors: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors: Syed A
authors: SA
authors: Ali
authors: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors: E Aubrey
authors: EA
authors: Thompson
authors: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
authors: Nicole R
authors: NR
authors: Murray
authors: Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA. Electronic address: fields.alan@mayo.edu.
authors: Alan P
authors: AP
authors: Fields
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D000099293:Protein Kinase C-lambda
chemical_list: D000217:Acyltransferases; D007527:Isoenzymes; D011493:Protein Kinase C; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; D000099293:Protein Kinase C-lambda; C527782:SOX2 protein, human; C105599:HHAT protein, human