Cytokeratins negatively regulate the invasive potential of lung cancer cell lines

Abstract

Abstract. Lung cancer cells express several cytokeratins (CKs) that are subdivided into type I (CK9-23) and type II (CK1-8) subclasses. The functions of CKs in lung cancer cells have not been fully elucidated. The purpose of this study was to investigate the role of CKs in the invasion of lung cancer cells. We investigated the expression levels of CK7, 8, 18 and 19 in 12 non-small cell lung cancer (NSCLC) and seven SCLC cell lines by quantitative immunoblotting. The expression levels of these four CKs were significantly higher in the NSCLC cells. The NSCLC cell line HI1017 expressed CK8 and 18; A549 cells expressed CK7, 8, 18 and 19, respectively. Invasive sublines of HI1017 and A549 were established by repeated selection of invasive cells using a membrane invasion chamber system. The invasive cell lines showed lower expression levels of CKs compared with the parental cells. Exogenous CK19 also resulted in a decrease in invasiveness of the HI1017 cells. Suppression of either CK8 or CK18 by short interfering RNAs led to a decrease in the total CKs and increased invasiveness of both the HI1017 and A549 cells. A549 cells expressed very low levels of CK19. Suppression of CK19 affected neither invasive ability nor total CK amount in the A549 cells. Our observations indicate that CK expression levels were inversely associated with invasiveness of the NSCLC cell lines, and suggest that expression levels of dominant CKs may affect invasive ability.

Keratin 8 and 18 Loss in Epithelial Cancer Cells Increases Collective Cell Migration and Cisplatin Sensitivity through Claudin1 Up-regulation

“…In a similar way, stable silencing of vimentin in squamous carcinoma cells resulted in re-emergence of keratins and a concomitant reduction in cell invasiveness and tumorigenic potential (57). Conversely, suppression of both K8/18 in non-small cell lung cancer cell lines increased their invasiveness (58). In the present study, we have demonstrated that K8/18 constitutes a signaling platform capable of moderating invasion and cell death in tumor cells.…”

Prognostic value of broad-spectrum keratin clones AE1/AE3 and CAM5.2 in small cell lung cancer patients undergoing pulmonary resection

“…Keratin expression in SCLC is weaker than in other lung cancer types, and the lack of its expression does not exclude the diagnosis of SCLC. The pathological data are corroborated by in vitro studies, which had shown that the levels of keratins expressed in SCLC cell lines were significantly lower than in the NSCLC lines (Kanaji et al, 2011). Among seven SCLC cell lines tested, only three (H69, H209 and Lu134) displayed K8 expression, and H209 were additionally characterized by K18 and K19 expression.…”

“…Despite their epithelial origin, some SCLCs are keratin-negative (Righi et al, 2017), which may sometimes cause clinically relevant diagnostic errors. The expression of keratins in SCLC is significantly lower than in the large cell neuroendocrine carcinoma (Nagashio et al, 2010) and nonsmall cell carcinoma (NSCLC) (Nobuhiro Kanaji et al, 2011), and the prognostic role of this feature in SCLC has not been extensively studied. AE1/AE3 is the most widely used antibody cocktail to detect cytokeratin expression.…”

Resolving an underrepresented circulating tumor cell population in lung cancer enabled by Hexokinase 2 analysis

“…Dying and stressed cells, as identified by the yellow cluster, exhibited extensive mitochondrial gene contamination and were removed from the subsequent analyses ( Fig CK7 and CK8 are highly expressed epithelial markers in NSCLC and are commonly used in cytopathological analysis of LUAD tumors (26,27). Reduced CK expression in cancer cells is often associated with loss of epithelial signatures and EMT processes (21).…”