LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer

Autor: Qing Chen, Peng-Sheng Zheng, Hao-Zhe Cao, Wen-Ting Yang, Xiao-Fang Liu
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Cellular pathology
Immunology
Green Fluorescent Proteins
Uterine Cervical Neoplasms
Antineoplastic Agents
Biology
medicine.disease_cause
Receptors
G-Protein-Coupled
Small hairpin RNA
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Cancer stem cell
Antigens
CD
Cell Movement
Genes
Reporter
Mice
Inbred NOD
Cell Line
Tumor
Spheroids
Cellular
medicine
Animals
Humans
Vimentin
Cell Proliferation
Cell Death
LGR5
Wnt signaling pathway
Cell migration
Cell Biology
Cadherins
Survival Analysis
Xenograft Model Antitumor Assays
Tumor Burden
Gene Expression Regulation
Neoplastic
030104 developmental biology
Cell culture
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Cancer research
Neoplastic Stem Cells
Female
Original Article
Cisplatin
Carcinogenesis
HeLa Cells
Signal Transduction
Zdroj: Cell Death & Disease
ISSN: 2041-4889
Popis: Cancer stem cells (CSCs), also known as tumor-initiating cells, contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) has recently been found to be a bona fide marker of colorectal CSCs. Our previous study showed that LGR5 functions as a tumor promoter in cervical cancer by activating the Wnt/β-catenin pathway. However, very little is known about the function or contribution of LGR5 to cervical CSCs. Here, we have modulated the expression of LGR5 using an overexpression vector or short hairpin RNA in cervical cancer cell lines. We demonstrated that elevated LGR5 expression in cervical cancer cells increased tumorsphere-forming efficiency; conferred chemoresistance to cisplatin treatment; augmented cell migration, invasion and clonogenicity; and elevated the levels of stem cell-related transcription factors in vitro. Furthermore, modulated LGR5+ cells, unlike LGR5− cells, were highly tumorigenic in vivo. In addition, the modulated LGR5+ cells could give rise to both LGR5+ and LGR5− cells in vitro and in vivo, thereby establishing a cellular hierarchy. Finally, we found that the increased tumorsphere-forming efficiency induced by LGR5 could be regulated through the inhibition or activation of the Wnt/β-catenin pathway in cervical cancer cells. Taken together, these results indicate that LGR5 has a vital oncogenic role by promoting cervical CSC traits and may represent a potential clinical target.
Databáze: OpenAIRE
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