COL11A1 is overexpressed in recurrent non-small cell lung cancer and promotes cell proliferation, migration, invasion and drug resistance

Abstract

Abstract. Collagen type XI α1 (COL11A1), a minor fibrillar collagen, has been demonstrated to be involved in cell proliferation, migration and the tumorigenesis of many human malignancies. Previous studies have shown that COL11A1 may be a valuable diagnostic marker for non-small cell lung carcinoma (NSCLC). However, its biological function in NSCLC progression remains largely unclear. In the present study, we investigated the expression levels of COL11A1 in different human NSCLC samples, and found that COL11A1 was overexpressed in NSCLC with lymph node metastasis and in recurrent NSCLC tissues. We also revealed that COL11A1 promoted the cell proliferation, migration and invasion of NSCLC cell lines in vitro. Furthermore, our results highlighted the importance of COL11A1 in chemoresistance to cisplatin. Mechanistically, we found that the effects of the overexpression of COL11A1 in NSCLC cells were mediated by Smad signaling. Collectively, our findings suggest that COL11A1 may sever as a biomarker for metastatic NSCLC, and can be used to predict recurrence after surgical resection. Therapeutic approaches targeting COL11A1 may facilitate the optimization of cisplatin treatment of NSCLC by overcoming chemoresistance. IntroductionLung cancer is the most common type of cancer, and is the leading cause of human cancer-related deaths (1,2). Non-small cell lung carcinoma (NSCLC) accounts for approximately 85% of all cases of human lung cancer, including all types of epithelial lung cancer except small cell lung carcinoma (SCLC) (3). Generally, the 5-year survival rate of lung cancer patients is approximately 15% (2). For patients with different stages of lung cancer, the 5-year relative survival rate varies dramatically from 49 to 2% (2,4). However, approximately 70% of patients with lung cancer were found to present with intrathoracic or extrathoracic metastasis at initial diagnosis (3,5). Thus, it is crucial to detect lung cancer at an early stage, and to suppress the spread of primary cancer.Currently, surgical resection remains the single most successful treatment for patients with early-stage NSCLC (6,7). However, despite optimal surgical treatment, approximately half of the patients with NSCLC develop recurrence and succumb to the disease, even though they present with histologically negative lymph nodes (8,9). While bone is the most common target of distant metastasis from lung cancer, recurrent NSCLC is often systemic (4,8). Although the mechanisms of recurrent NSCLC remain unclear, several molecules have been reported to predict the recurrence of NSCLC. These include EphA2 (EPH receptor A2) receptor tyrosine kinase, USP17 and DNA methylation markers (10-12).The collagen type XI α1 (COL11A1) gene encodes one of the two α chains of type XI collagen, a minor fibrillar collagen (13). As a major component of the extracellular matrix (ECM), collagens are involved in the regulation of multiple biological processes, including cell proliferation, differentiation and migration (14,15). Type XI collagen is a heterotrimer, ...

B-Myb Is Up-Regulated and Promotes Cell Growth and Motility in Non-Small Cell Lung Cancer

“…Thus, it is highly likely that a B-Myb-CCNA1 regulatory loop also exists and plays an important role in NSCLC cells. COL11A1 , COL6A1 , MMP2 , NID1 , and FLT4 have been shown to have a positive role in regulating motility and invasion of various cancer cells [26,27,28,29,30,31]. Moreover, we also found that the deregulated genes affected by B-Myb overexpression could be enriched in ERK and Akt signaling pathways.…”

Integrated bioinformatics analysis of key genes involved in progress of colon cancer

“…In lung cancer, it has a positive correlation with pathology stage, poor prognosis, and lymph node metastasis (Chong et al, ), it promotes ovarian cancer progression and chemoresistance to cisplatin and paclitaxel via activating NF‐KB , and it promotes the expression of TWIST1 , MCL1( Wu, Huang, Chang, & Chou, ). It has also been reported that COL11A1 was upregulated in gastric cancer and non‐small cell lung cancer which could boost the malignant behavior in vitro (Li, Li, Lin, Zhuo, & Si, ; Shen et al, ). COL11A1 could be utilized as a promising biomarker in predicting malignant relapse of breast intraductal papilloma (Freire et al, ).…”

Systematical identifications of prognostic meaningful lung adenocarcinoma subtypes and the underlying mutational and expressional characters

“…Here, the significant mutations of SMARCA4 were also related with the poor survival rate of one LUAD subtype (Figure 4), and the mutations may lead to decreased expressions of SMARCA4 (see Additional file 1). Similarly, KEAP1 [40], TP53 [41] and COL11A1 [33] have all been reported to play roles in LUAD. Co-occurrence of these SMGs in the poor survival subtype implies that the differential prognosis between the two subtypes is not simply the result of one specific gene but a collection of meaningful genes.…”