Atypical protein kinase Cτ plays a critical role in human lung cancer cell growth and tumorigenicity

Roderick P. Regala, Capella Weems, Lee Jamieson, John A III Copland, E Aubrey Thompson, Alan P Fields

Research output: Contribution to journalArticle

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Abstract

Atypical protein kinase C (aPKC) isozyimes function in epithelial cell polarity, proliferation, and survival and have been implicated in cellular transformation. However, the role of these enzymes in human cancer is largely unexplored. Here, we report that aPKCτ is highly expressed in human non-small cell lung cancer cell lines, whereas the closely related aPKC isozyme PKCζ is undetectable in these cells. Disruption of PKCτ signaling reveals that PKCτ is dispensable for adherent growth of non-small cell lung cancer cells but is required for transformed growth in soft agar in vitro and for tumorigenicity in vivo. Molecular dissection of signaling downstream of PKCτ demonstrates that Rac1 is a critical molecular target for PKCτ-dependent transformation, whereas PKCτ is not necessary for NFκB activation in vitro or in vivo. Expression of the PB1 domain of PKCi (PKCτ-(1-113)) blocks PKCτ-dependent Rac1 activity and inhibits cellular transformation indicating a role for this domain in the transforming activity of PKCτ. Taken together, our data demonstrate that PKCτ is a critical lung cancer gene that activates a Rac1→Pak→Mek1,2→Erk1,2 signaling pathway required for transformed growth. Our data indicate that PKCτ may be an attractive molecular target for mechanism-based therapies for treatment of lung cancer.

Original languageEnglish (US)
Pages (from-to)31109-31115
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number35
DOIs
StatePublished - Sep 2 2005

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Cell growth
Lung Neoplasms
Cells
Non-Small Cell Lung Carcinoma
Growth
Cell Polarity
Neoplasm Genes
Dissection
Isoenzymes
Agar
Cell Survival
Epithelial Cells
Cell Proliferation
Cell Line
Genes
Chemical activation
Enzymes
PKC-3 protein
Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

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Atypical protein kinase Cτ plays a critical role in human lung cancer cell growth and tumorigenicity. / Regala, Roderick P.; Weems, Capella; Jamieson, Lee; Copland, John A III; Thompson, E Aubrey; Fields, Alan P.

In: Journal of Biological Chemistry, Vol. 280, No. 35, 02.09.2005, p. 31109-31115.

Research output: Contribution to journalArticle

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