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

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

  • Cancer Cell. 2014 Feb 10;25(2):139-51. doi: 10.1016/j.ccr.2014.01.008.
Verline Justilien 1,  Michael P Walsh 1,  Syed A Ali 1,  E Aubrey Thompson 1,  Nicole R Murray 1,  Alan P Fields 2
Affiliations

Affiliations

  • 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: [email protected].
PMID: 24525231 DOI: 10.1016/j.ccr.2014.01.008
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.

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