RRC ID 54776
Author Kosibaty Z, Murata Y, Minami Y, Dai T, Kano J, Matsuoka R, Nakano N, Noguchi M.
Title Cytoplasmic expression of epithelial cell transforming sequence 2 in lung adenocarcinoma and its implications for malignant progression.
Journal Lab. Invest.
Abstract Epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor, is predominantly localized in the nucleus of non-transformed cells and functions to regulate cytokinesis. ECT2 is also localized in the cytoplasm of cancer cells. Aberrant cytoplasmic expression of ECT2 is thought to drive tumor growth and invasion. In this study, we investigated the cytoplasmic expression of ECT2 and its prognostic and biological significance in lung adenocarcinoma. Western blotting of cellular fractions from the nucleus and cytoplasm was performed to determine the subcellular localization of ECT2 in lung adenocarcinoma cell lines. The cytoplasmic expression of ECT2 in 167 lung adenocarcinomas was evaluated by immunohistochemistry and its clinical significance was examined using Kaplan-Meier curves and Cox regression analysis. Scraping cytology specimens of 13 fresh lung adenocarcinomas were used to assess the subcellular localization of ECT2 and its phosphorylation at Thr790 (P-ECT2(T790)). We found that ECT2 was localized in both the nucleus and cytoplasm of lung adenocarcinoma cell lines and tumor tissues. Cytoplasmic expression of ECT2 was detected by immunohistochemistry in 83 (50%) of the lung adenocarcinomas, and was found to increase during cancer progression. It was expressed in 30 (29%) small adenocarcinomas ( ≤ 2 cm in diameter) and 53 (82%) advanced adenocarcinomas ( > 2 cm in diameter). Cytoplasmic positivity for ECT2 was associated with a poor outcome in terms of both disease-free and overall survival (both P < 0.001), and was an independent prognostic factor for overall survival (P = 0.025). Immunocytochemical staining for P-ECT2(T790) demonstrated cytoplasmic and membrane positivity in Calu-3 cells and scraping cytology specimens. Positive P-ECT2(T790) staining was correlated with cytoplasmic ECT2 expression in 6 of 13 scraped cytology specimens tested. In conclusion, our findings indicate that cytoplasmic ECT2 expression could promote the malignant progression of lung adenocarcinoma and may represent a potent therapeutic target for patients with lung adenocarcinoma.
Volume 99(4)
Pages 551-567
Published 2019-4
DOI 10.1038/s41374-018-0142-4
PII 10.1038/s41374-018-0142-4
PMID 30542068
MeSH Adenocarcinoma of Lung / metabolism* Adenocarcinoma of Lung / pathology Cell Line, Tumor Cytoplasm / chemistry Cytoplasm / metabolism* Disease Progression Disease-Free Survival Female Gene Knockdown Techniques Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology Male Middle Aged Prognosis Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism*
IF 3.684
Human and Animal Cells PC-9(RCB4455) RERF-LC-KJ(RCB1313)