The PRKCI and SOX2 Oncogenes Are Coamplified and Cooperate to Activate Hedgehog Signaling in Lung Squamous Cell Carcinoma

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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.

Original languageEnglish (US)
Pages (from-to)139-151
Number of pages13
JournalCancer Cell
Volume25
Issue number2
DOIs
StatePublished - Feb 10 2014

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Acyltransferases
Oncogenes
Protein Kinase C
Squamous Cell Carcinoma
Lung
Phenotype
Carcinogenesis
Chromosomes
Maintenance
Phosphorylation
Ligands
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

@article{b3d34b45b1b849fd9fb7f3b7911ee81e,
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.",
author = "Verline Justilien and Walsh, {Michael P.} and Ali, {Syed A.} and Thompson, {E Aubrey} and Murray, {Nicole R} and Fields, {Alan P}",
year = "2014",
month = "2",
day = "10",
doi = "10.1016/j.ccr.2014.01.008",
language = "English (US)",
volume = "25",
pages = "139--151",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

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TY - JOUR

T1 - The PRKCI and SOX2 Oncogenes Are Coamplified and Cooperate to Activate Hedgehog Signaling in Lung Squamous Cell Carcinoma

AU - Justilien, Verline

AU - Walsh, Michael P.

AU - Ali, Syed A.

AU - Thompson, E Aubrey

AU - Murray, Nicole R

AU - Fields, Alan P

PY - 2014/2/10

Y1 - 2014/2/10

N2 - 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.

AB - 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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