OBJECTIVES: Actin-associated proteins at cell-matrix-contact sites form invadopodia in cancer cells and participate in migration, matrix degradation and invasion. We investigated an alteration of subcellular localization of invadopodia-related actin-associated proteins, actinin-1 and cortactin, in lung adenocarcinomas, its clinical significance, and its possible regulatory factors. METHODS: Invadopodia-related proteins, actinin-1 and cortactin, were immunohistochemically examined in 90 cases of lung adenocarcinomas. Expression of invadopodia-associated proteins and their possible regulators in lung adenocarcinomas were examined by real-time RT-PCR, database search, and immunohistochemistry. RESULTS: Actinin-1 and cortactin showed matrix-contact-side localization in adenocarcinoma cells, but rarely in normal bronchiolar epithelial cells, alveolar cells, or precursor lesion atypical adenomatous hyperplasia cells. Immunoelectron-microscopic examination of adenocarcinoma cells revealed actinin-1 localization to matrix-contact-side cytoplasm with cytoplasmic protrusions. Matrix-contact-side localization of actinin-1 and cortactin was correlated with tumor stages, lymph node metastasis, vascular permeation, and loss of basement membrane. The tumor-specific survival rate was worse for the group in which matrix-contact-side localization of cortactin was high than for the low group. mRNA of the Rho guanine exchange factor epithelial cell transforming sequence-2 (Ect2) tended to be overexpressed in lung adenocarcinomas and cytoplasmic expression of Ect2 tended to be correlated with matrix-contact-side localization of actinin-1. CONCLUSION: Matrix-contact-side localization of invadopodia-related proteins in the lung adenocarcinoma cells were correlated with invasion, metastasis, and poor prognosis. Ect2 was a possible regulator of matrix-contact-side localization of invadopodia-related proteins.
OBJECTIVES: Actin-associated proteins at cell-matrix-contact sites form invadopodia in cancer cells and participate in migration, matrix degradation and invasion. We investigated an alteration of subcellular localization of invadopodia-related actin-associated proteins, actinin-1 and cortactin, in lung adenocarcinomas, its clinical significance, and its possible regulatory factors. METHODS: Invadopodia-related proteins, actinin-1 and cortactin, were immunohistochemically examined in 90 cases of lung adenocarcinomas. Expression of invadopodia-associated proteins and their possible regulators in lung adenocarcinomas were examined by real-time RT-PCR, database search, and immunohistochemistry. RESULTS:Actinin-1 and cortactin showed matrix-contact-side localization in adenocarcinoma cells, but rarely in normal bronchiolar epithelial cells, alveolar cells, or precursor lesion atypical adenomatous hyperplasia cells. Immunoelectron-microscopic examination of adenocarcinoma cells revealed actinin-1 localization to matrix-contact-side cytoplasm with cytoplasmic protrusions. Matrix-contact-side localization of actinin-1 and cortactin was correlated with tumor stages, lymph node metastasis, vascular permeation, and loss of basement membrane. The tumor-specific survival rate was worse for the group in which matrix-contact-side localization of cortactin was high than for the low group. mRNA of the Rho guanine exchange factor epithelial cell transforming sequence-2 (Ect2) tended to be overexpressed in lung adenocarcinomas and cytoplasmic expression of Ect2 tended to be correlated with matrix-contact-side localization of actinin-1. CONCLUSION: Matrix-contact-side localization of invadopodia-related proteins in the lung adenocarcinoma cells were correlated with invasion, metastasis, and poor prognosis. Ect2 was a possible regulator of matrix-contact-side localization of invadopodia-related proteins.
Authors: Yujia Wen; Eric R Gamazon; Wasim K Bleibel; Claudia Wing; Shuangli Mi; Bridget E McIlwee; Shannon M Delaney; Shiwei Duan; Hae Kyung Im; M Eileen Dolan Journal: Hum Mol Genet Date: 2011-12-13 Impact factor: 6.150
Authors: Carman Man-Chung Li; Guoan Chen; Talya L Dayton; Caroline Kim-Kiselak; Sebastian Hoersch; Charles A Whittaker; Roderick T Bronson; David G Beer; Monte M Winslow; Tyler Jacks Journal: Genes Dev Date: 2013-07-15 Impact factor: 11.361
Authors: Ce Li; Zhenzi Peng; Yizhou Wang; Gloria Lam; Nicholas Nissen; Jie Tang; Xiaopu Yuan; Michael Lewis; Mark I Greene; Stephen J Pandol; Qiang Wang Journal: Am J Physiol Gastrointest Liver Physiol Date: 2021-01-27 Impact factor: 4.052