Abstract
BackgroundTetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion.MethodsFirst, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied.ResultsHigh CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs.ConclusionsBased on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment.
Highlights
Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers
Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting Epidermal growth factor receptor (EGFR)/ErbB2 signaling pathway, by which CD151 promotes non-small cell lung cancer (NSCLC) proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment
CD151 is highly expressed in NSCLC tissues and cell lines and its elevated expression is correlated with poor prognosis Immunohistochemistry (IHC) analysis was carried out to evaluate CD151 protein level in 150 paired NSCLC tissues
Summary
Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. The precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Lung cancer is the most frequent cause of cancer-related deaths worldwide [1, 2]. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancers [3]. Tetraspanins are four-transmembrane-spanning proteins containing short cytoplasmic N- and C-termini and one small and one large extracellular domain, which are highly expressed on cell surface or intracellular vesicle [5]. The most important character of tetraspanins is that they form complexes by interacting with each other and/ or other transmembrane proteins, including integrins, RTK (EGFR and c-Met), cytoskeleton and cytosolic signal transduction molecule [6]. Tetraspanins are considered as regulators of cellular signaling and are often depicted as molecular facilitators [7]
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