A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) metastasis is driven by lung cancer stem cell-like cells (LCSCs), but the underlying mechanisms remain unclear. Here, we aim to investigate biological function of CD44 in regulating metastatic trait of LCSCs and its underlying mechanisms. In this study, we found that CD133 CD44 cells which were derived from primary lung adenocarcinoma (LAC) possessed cancer stem cell-like features. Furthermore, CD44 was demonstrated functionally crucial to drive metastatic potential of CD133 CD44 LCSCs by in vitro and in vivo experiments. In patient cohorts, high level of CD44 predicted increased probability of metastasis. Significantly, microarray revealed that FoxM1 and key proteins of Wnt/β-catenin pathway were up-regulated in CD133 CD44 LCSCs compared with those in CD133 CD44 cells. Then, we demonstrated that CD44 promoted metastatic activity in CD133 CD44 LCSCs through Wnt/β-catenin pathway and FoxM1 was the downstream target of Wnt/β-catenin pathway. Meanwhile, our findings indicated that FoxM1 promoted metastatic activity in CD133 CD44 LCSCs by inducing EMT and Twist was a direct transcriptional target of FoxM1. Collectively, CD44, both a functional biomarker and therapeutic target, promoted CD133 CD44 LCSCs metastasis by Wnt/β-catenin-FoxM1-Twist signaling. This study provided support for the missing link between EMT and CSCs surface-marker and supplied a promising approach for elimination of LCSCs by targeting CD44-Wnt/β-catenin-FoxM1-Twist signaling. © 2015 Wiley Periodicals, Inc.

Background: MicroRNAs (miRNAs) play important roles in many biological processes, including cancer development. Among those miRNAs, miR-143 shows tumor-suppressive activity in some human cancers. However, the function and mechanism of miR-143 in lung cancer cells remains unknown. Here we explored the role of miR-143 in lung cancer. Results: According to qRT-PCR, we found that miR-143 was notably down-regulated in 19 NSCLC tissues and 5 cell lines. In vitro experiments showed us that miR-143 could significantly suppress the migration and invasion of NSCLC cell lines while it had no effects on the growth of NSCLC cell lines, and in vivo metastasis assay showed the same results. Finally, we found that the mechanism of miR-143 inhibiting the migration and invasion of NSCLC might be through targeting CD44v3. Conclusions: The up-regulated miR-143 in lung cancer could significantly inhibit cell migration and invasion, and this might work through targeting CD44v3, which was newly identified by us.

Drugs derived from traditional Chinese medicines (TCM) include both single chemical entities and multi-component preparations.

Platinum-based chemotherapies have long been used as a standard treatment in non-small cell lung cancer (NSCLC). However, cisplatin resistance is a major problem that restricts the use of cisplatin. Lung cancer stem cells (LCSCs) represent a subpopulation that is responsible for chemo-resistance. We aim to investigate the biological function of SLC27A2 and its underlying mechanisms in regulating chemo-resistance to cisplatin in LCSCs. Here, our findings testified that CD166 cells which were derived from fresh primary NSCLC samples displayed stem cell-like features and were resistant to chemotherapy drug cisplatin. In patient cohort, we found the presence of a variable fraction of CD166 cells in 24 out of 25 primary NSCLC samples. Significantly, SLC27A2 expression was reduced in CD166 LCSCs. Reduced SLC27A2 correlated chemo-response and poor patient survival. Our results indicated that enhanced SLC27A2 expression sensitized CD166 LCSCs to cisplatin by in vitro and in vivo experiments. Microarray profiling showed that the expression of Bmi1 and ABCG2 was enhanced in p-SLC27A2-LCSCs compared with that in pc3.1DNA-LCSCs. Furthermore, we demonstrated that reduced SLC27A2 induced chemo-resistance in CD166 LCSCs by negatively regulating Bmi1-ABCG2 signaling, and ABCG2 was a direct transcriptional target of Bmi1. Thus, this study widens the window for identification and targeting of a cisplatin-resistant population and contributes to the development of potential therapeutics to improve the current treatment modalities in NSCLC. © 2015 Wiley Periodicals, Inc.