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Cancer Cell. 2014 Feb 10;25(2):139-51. doi: 10.1016/j.ccr.2014.01.008.

The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma.

Author information

1
Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA.
2
Department of Cancer Biology, Mayo Clinic Cancer Center, Jacksonville, FL 32224, USA. Electronic address: fields.alan@mayo.edu.

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.

PMID:
24525231
PMCID:
PMC3949484
DOI:
10.1016/j.ccr.2014.01.008
[Indexed for MEDLINE]
Free PMC Article

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