Author of

• 11454

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  P2.01 - Poster Session 2 - Cancer Biology (ID 145)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11463

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    P2.01-009 - Altered expression of aPKC lambda/iota and Lgl2 correlates with invasion and metastasis in lung adenocarcinoma (ID 3261)

    09:30 - 09:30  |  Author(s): Y. Horikoshi
    • Abstract

    Background
    Many early-stage NSCLCs in spite of treating with surgical resection and adjuvant therapy relapse, occur metastasis and become fatal. Therefore there is an urgent need for research the key molecular events driving lung cancer invasion and metastasis that could lead to achieve effective prevention, reliable diagnosis, preparing useful prognostic indicator and treatment. Atypical protein kinase C lambda/iota (aPKCλ/℩), Partitioning defective-3 (Par3), Partitioning defective-6 (Par6) and Drosophila Lethal giant larvae mammalian homologue (Lgl2) are implicated in cell growth and apoptosis, and the maintenance of epithelial cell polarity. Loss of apical-basal polarity in epithelial cells is one of the hallmarks of aggressive and invasive cancer. This study was designed to investigate the correlation of expression of aPKCλ/℩ and Lgl2 with the clinicopathological characteristics and prognosis of lung adenocarcinoma, and to analyze the molecular mechanisms of invasion and metastasis of the tumor.

    Methods
    This study included 107 patients who underwent resection of lung tumor and diagnosed as lung adenocarcinoma at the Tokai University Hospital between 2002 and 2005. The expression of aPKCλ/℩ and Lgl2 was examined by immunohistochemistry. E-cadherin-mediated cell-cell adhesion is considered a suppressor of cancer cell invasion. Low E-cadherin expression in NSCLC tumors has been reported in several studies to be associated with a more aggressive behavior of tumor cells and a worse prognosis. In this study, the colocalization of aPKCλ/℩ and E-cadherin was observed by double-immunohistochemistry. Furthermore, we also analyzed the interaction of aPKCλ/℩, Par3 and Lgl2 by immunoprecipitation-Western blot assays.

    Results
    Immunohistochemical analysis showed that aPKCλ/℩ and Lgl2 were expressed in lung adenocarcinoma and correlated with lymphatic invasion and metastasis. Kaplan-Meier regression analysis showed that patients with　increased aPKCλ/℩　expression had significantly shorter overall survival than those with lower aPKCλ/℩ expression. Double-immunohistochemistry showed E-cadherin decreased in highly expressed aPKCλ/℩ of tumor cells. Furthermore, immunoprecipitation-Western blot assays showed that aPKCλ/℩-Lgl2-Par6 complex and　aPKCλ/℩-Par3-Par6 complex increased in lung adenocarcinoma tissue.

    Conclusion
    These results suggested that aberrant formation of both aPKCλ/℩-Lgl2-Par6 complex and aPKCλ/℩-Par3-Par6 complex could induce lung cancer progression by loss of cell-cell adhesion in lung adenocarcinoma.