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Wnt signaling regulation of stem-like properties in human lung adenocarcinoma cell lines

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Abstract

The refractory pulmonary adenocarcinoma is characterized by its metastasis and resistance to cytotoxic agents. While the underlying molecular mechanism is unclear, the property of chemoresistance may mainly lie in the presence of highly resistant cancer stem cells. We examined the function of Wnt/β-catenin signaling in maintaining cancer stem cells (CSCs) in lung adenocarcinoma. Lentivirus-mediated knockdown of β-catenin expression accelerated cell cycle. Subsequently, β-catenin knockdown PC9 cells improve the sensitivity to chemotherapy. Further focusing on Wnt signal by administrating PP and EGFR-TKIs as Wnt antagonists can decrease metastasis and induce apoptosis. Collectively, these results indicate that Wnt signaling pathway plays an essential role in maintaining highly resistant CSCs, regulation of cell cycle, metastasis and apoptosis in lung adenocarcinoma.

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Abbreviations

LRP:

Lipoprotein receptor-related protein

APC:

Adenomatous polyposis coli

GSK-3:

Glycogen synthase kinase 3

RSpo2:

R-spondin 2

CK1:

Casein kinase 1

FZD:

Frizzled

TCF:

T-cell factor

LEF:

Lymphoid enhancer factor

EGFR-TKIs:

Tyrosine kinase inhibitors

LDCs:

Label dilution cells

PBS:

Phosphate buffer saline

ALDH:

Aldehyde dehydrogenase

TTF1:

Thyroid transcription factor 1

BIO:

6-Bromoindirubin-3′-oxime

DMEM:

Dulbecco’s modification of Eagle’s medium

BCRP/ABCG2:

Breast cancer resistance protein

LGR:

Leucine-rich repeat G-protein-coupled receptors

β-KD PC9 cells:

β-catenin knockdown PC9 cells

EGFR:

Epidermal growth factor receptor

CMI:

CFSE mean intensity

LRCs:

Label-retaining cells

FBS:

Fetal bovine serum

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Acknowledgments

We thank the staff in Flow Cytometry Department of Shanghai Jiao Tong University, School of Medicine for their work. This work was supported by grants from the Shanghai Natural Science Foundation of China (13ZR1438600).

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Authors and Affiliations

  1. Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, 25/Ln 2200 Xietu Road, Shanghai, 200032, People’s Republic of China

    Yan Zhang & Qianggang Dong

  2. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine, 241 Huaihai Road (West), Shanghai, 200030, People’s Republic of China

    Xueyan Zhang & Jinsu Huang

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  1. Yan Zhang
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Correspondence to Qianggang Dong.

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Zhang, Y., Zhang, X., Huang, J. et al. Wnt signaling regulation of stem-like properties in human lung adenocarcinoma cell lines. Med Oncol 32, 157 (2015). https://doi.org/10.1007/s12032-015-0596-9

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  • DOI: https://doi.org/10.1007/s12032-015-0596-9

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