title: Localization of aPKC lambda/iota and its interacting protein, Lgl2, is significantly associated with lung adenocarcinoma progression.
abstract: Atypical protein kinase C lambda/iota (aPKC λ/ι) is expressed in several human cancers; however, the correlation between aPKC λ/ι localization and cancer progression in human lung adenocarcinoma (LAC) remains to be clarified. We found that patients with a high level of aPKC λ/ι expression in LAC had significantly shorter overall survival than those with a low level of aPKC λ/ι expression. In addition, localization of aPKC λ/ι in the apical membrane or at the cell-cell contact was associated with both lymphatic invasion and metastasis. The intercellular adhesion molecule, E-cadherin, was decreased in LACs with highly expressed aPKC λ/ι at the invasion site of tumor cells. This result suggested that the expression levels of aPKC λ/ι and E-cadherin reflect the progression of LAC. On double-immunohistochemical analysis, aPKC λ/ι and Lgl2, a protein that interacts with aPKC λ/ι, were co-localized within LACs. Furthermore, we found that Lgl2 bound the aPKC λ/ι-Par6 complex in tumor tissue by immune-cosedimentation analysis. Apical membrane localization of Lgl2 was correlated with lymphatic invasion and lymph node metastasis. These results thus indicate that aPKC λ/ι expression is altered upon the progression of LAC. This is also the first evidence to show aPKC λ/ι overexpression in LAC and demonstrates that aPKC λ/ι localization at the apical membrane or cell-cell contact is associated with lymphatic invasion and metastasis of the tumor.
authors: Naoko
authors: N
authors: Imamura
authors: Yosuke
authors: Y
authors: Horikoshi
authors: Tomohiko
authors: T
authors: Matsuzaki
authors: Kentaro
authors: K
authors: Toriumi
authors: Kanae
authors: K
authors: Kitatani
authors: Go
authors: G
authors: Ogura
authors: Ryota
authors: R
authors: Masuda
authors: Naoya
authors: N
authors: Nakamura
authors: Susumu
authors: S
authors: Takekoshi
authors: Masayuki
authors: M
authors: Iwazaki
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult; D000099293:Protein Kinase C-lambda
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda; C526122:llgl2 protein, human