The effects and mechanisms of SLC34A2 on tumorigenicity in human non-small cell lung cancer stem cells
| Autor: | Xueqiang Wei, Peng Liu, Yanhong Hao, Xiaoquan Ding, Junfeng Xi, Zhanxin Jiang, Zhibin Zhang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Lung Neoplasms Carcinogenesis Mice Nude Cell Separation Biology medicine.disease_cause Real-Time Polymerase Chain Reaction Sodium-Phosphate Cotransporter Proteins Type IIb Flow cytometry 03 medical and health sciences Mice 0302 clinical medicine Carcinoma Non-Small-Cell Lung medicine Animals Humans Lung cancer Wnt Signaling Pathway Mitogen-Activated Protein Kinase 7 Aged Mice Inbred BALB C medicine.diagnostic_test Wnt signaling pathway Cancer General Medicine Cell sorting Middle Aged medicine.disease Flow Cytometry 030104 developmental biology BMI1 030220 oncology & carcinogenesis Cancer research Neoplastic Stem Cells Heterografts Female Stem cell |
| Zdroj: | Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 37(8) |
| ISSN: | 1423-0380 |
| Popis: | A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but molecular mechanisms regulating tumorigenic and self-renewal potential of LCSCs are still unclear. Here, we aim to investigate biological function of SLC34A2 in regulating tumorigenicity of LCSCs and its underlying mechanisms. Our findings testified that CD166(+) cells which were derived from fresh primary NSCLC samples displayed stem cell-like features. Fluorescence-activated cell sorting (FACS) analysis showed the presence of a variable fraction of CD166 cells in 15 out of 15 NSCLC samples. Significantly, CD166(+) LCSCs from primary NSCLC tumors expressed high level of SLC34A2 which was required for CD166(+) LCSCs tumorigenic and self-renewal potential. In NSCLC patient cohort, increased SLC34A2 expression correlated with histology, which suggests a potential role of SLC34A2 in CD166(+) LCSCs. Furthermore, Wnt/β-catenin pathway and Bmi1 were found necessary for tumorigenicity and self-renewal capacity of CD166(+) LCSCs by a series in vitro and in vivo experiments. Then, our study indicated that SLC34A2 regulated Bmi1 to promote tumorigenic and self-renewal potential of CD166(+) LCSCs through Wnt/β-catenin pathway. In this study, the characterization of molecular basis of SLC34A2 in CD166(+) LCSCs not only allows for better understanding of the mechanisms regulating tumorigenicity of this specific population of NSCLC cells but also provides insight into the gradual improvement of more effective cancer therapies against this disease. |
| Databáze: | OpenAIRE |
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