FGF1 and IGF1-conditioned 3D culture system promoted the amplification and cancer stemness of lung cancer cells

Liu, Pengpeng; Zhang, Rui; Yu, Wenwen; Ye, Yingnan; Cheng, Yanan; Han, Lei; Dong, Li; Chen, Yongzi; Wei, Xuedong; Yu, Jinpu

doi:10.1016/j.biomaterials.2017.09.030

Cited by 35 publications

(41 citation statements)

References 72 publications

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“…All these detections of cellular functions were performed according to the manufacturer's protocol as previously described (27). And the experiments were repeated at least 3 times.…”

Section: Detection Of Cell Proliferation Cell Apoptosis Analysis Womentioning

confidence: 99%

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LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY

Zhang

Sun

et al. 2019

Cancer Research

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Somatic long interspersed element-1 (LINE-1) retrotransposition is a genomic process that relates to gene disruption and tumor occurrence. However, the expression and function of LINE-1 retrotransposition in lung squamous cell carcinoma (LUSC) remain unclear. We analyzed the transcriptomes of LUSC samples in The Cancer Genome Atlas and observed LINE-1 retrotransposition in 90% of tumor samples. Thirteen LINE-1 retrotranspositions of high occurrence were identified and further validated from an independent Chinese LUSC cohort. Among them, LINE-1-FGGY (L1-FGGY) was identified as the most frequent LINE-1 retrotransposition in the Chinese cohort and significantly correlated with poor clinical outcome. L1-FGGY occurred with smoke-induced hypomethylation of the LINE-1 promoter and contributed to the development of local immune evasion and dysfunctional metabolism. Over-expression of L1-FGGY or knockdown of FGGY promoted cell proliferation and invasion in vitro, facilitated tumorigenesis in vivo, and dysregulated cell energy metabolism and cytokine/ chemotaxin transcription. Importantly, specific reverse transcription inhibitors, nevirapine and efavirenz, dramatically countered L1-FGGY abundance, inhibited tumor growth, recovered metabolism dysfunction, and improved the local immune evasion. In conclusion, hypomethylation-induced L1-FGGY expression is a frequent genomic event that promotes the development and progression of LUSC and represents a promising predictive biomarker and therapeutic target in LUSC. Significance: LINE-1-FGGY is a prognosis predictive biomarker and potential therapeutic target to overcome local immune evasion in lung squamous cell carcinoma.

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“…All these detections of cellular functions were performed according to the manufacturer's protocol as previously described (27). And the experiments were repeated at least 3 times.…”

Section: Detection Of Cell Proliferation Cell Apoptosis Analysis Womentioning

confidence: 99%

“…RNA extraction, cDNA synthesis, retrotransposition-PCR, and regular qPCR analysis were performed following the manufacturer's protocol as previously described (27). The sequences of primers are shown in Supplementary Table S1.…”

Section: Rna Extraction Retrotransposition-pcr and Qpcr Analysis Fomentioning

confidence: 99%

LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY

Zhang

Sun

et al. 2019

Cancer Research

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“…Lung CSCs play an important role in tumour metastasis and recurrence. In this study, the tumour spheres derived from parental A549 cells overexpressed stemness‐associated markers including CD133, Nanog, Sox2 and ALDH1, which are associated with the lung CSC phenotype 23,24 . The gold standard for the differentiation of CSCs from parental cancer cells is the capacity for self‐renewal 25 .…”

Section: Discussionmentioning

confidence: 90%

Lung CSC‐derived exosomal miR‐210‐3p contributes to a pro‐metastatic phenotype in lung cancer by targeting FGFRL1

Wang

et al. 2020

J Cellular Molecular Medi

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Lung cancer has the highest mortality rate among human cancers, and the majority of deaths can be attributed to metastatic spread. Lung cancer stem cells (CSCs) are a component of the tumour microenvironment that contributes to this process. Exosomes are small membrane vesicles secreted by all types of cells that mediate cell interactions, including cancer metastasis. Here, we show that lung CSC‐derived exosomes promote the migration and invasion of lung cancer cells, up‐regulate expression levels of N‐cadherin, vimentin, MMP‐9 and MMP‐1, and down‐regulate E‐cadherin expression. Moreover, we verified that these exosomes contribute to a pro‐metastatic phenotype in lung cancer cells via miR‐210‐3p transfer. The results of bioinformatics analysis and dual‐luciferase reporter assays further indicated that miR‐210‐3p may bind to fibroblast growth factor receptor‐like 1 (FGFRL1); silencing FGFRL1 enhanced the metastatic ability of lung cancer cells, whereas overexpressing FGFRL1 suppressed metastasis. Taken together, our results provide new insights into a potential molecular mechanism whereby lung CSC‐derived exosomal miR‐210‐3p targets FGFRL1 to promote lung cancer metastasis. FGFRL1 may be a promising therapeutic target in lung cancer.

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“…Overexpression of FGF1 stimulates the dissemination of breast cancer and leads to the metastasis of cancer 19 .Using a FGF-1-speci c single-chain antibody, the growth and metastasis tendency of breast cancer was signi cantly restrained 27 . Lung cancer stem cells exhibited increased proliferative potential, enhanced tumorigenic activity, upregulated epithelial-to-mesenchymal transition under FGF1-based 3D culture 17 . Although the clinical relevance of FGF1 has been described in various cancers, its role in NPC development and progression has not been discussed.…”

Section: Discussionmentioning

confidence: 99%

“…FGF1 is a member of Fibroblast growth factor family and stimulates downstream signaling cascades via binding and phosphorylating the FGFR1/2, a transmembrane tyrosine kinase that act as docking sites for interacting proteins. Accumulating evidences indicate that FGF1 promotes tumor development by facilitating cell proliferation, migration, invasion and angiogenesis [16][17][18] . Aberrant expression of FGF1 has been found in a variety of human cancers, such as breast cancer, bladder cancer, hepatocellular carcinoma, ovarian cancer, pancreatic cancer, and proved to stimulate the development of these tumors [19][20][21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

LHX2 facilitates the progression of nasopharyngeal carcinoma via activating the autocrine secretion of FGF1

Xie¹,

Wang²,

Zheng³

et al. 2020

Preprint

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Background: Distant metastasis and recurrence remain the obstacle for nasopharyngeal carcinoma (NPC) treatment in clinical, unfortunately, the molecular events underlying NPC growth and metastasis are poorly understood. Methods: The expression level and prognostic value of LHX2 in pan-cancer were analized in TCGA database. The LHX2 expression both in protein and RNA levels in NPC tissues and normal tissues was determined by western blot, qRT-PCR and immunohistochemistry. The roles of LHX2 in oncogenesis were determined using CCK-8, colony formation assays, EdU assay, wound healing assays,transwell assay as well as in vivo mouse model.Bioinformatics analysis, the Gene Set Enrichment Analysis, Luciferase Reporter Assays and Chromatin Immunoprecipitation Assays were applied to identify the downstream effector of LHX2. The activation of indicated signal pathways were measured by western blot. Results: The LIM-homeodomain transcription factor 2 (LHX2) expression was increased in many solid tumors and was associated with poor progression based on the data from TCGA database.LHX2 levels was also significantly upregulated in NPC tissues and cell lines.Ectopic expression of LHX2 dramatically promoted the cell viability, colony formation efficiency, migratory and invasive ability of NPC cells both in vitro and in vivo. In mechanism, the Fibroblast Growth Factor 1 (FGF1) was confirmed transcriptionally regulated by LHX2 and mediated LHX2-induced tumor-promoting effects. The elevated expression of FGF1 by LHX2 activated the phosphorylation of STAT3, ERK1/2 and AKT/ser9-GSK3β/β-catenin signal pathway, leading to the increased proliferation ability and epithelial-to-mesenchymal transition (EMT). Treating NPC cells with FGF1-conditioned medium or human recombinant FGF1 accelerated tumor growth and metastasis, which could be blocked by tyrosine kinase inhibitor, AZD4547. \Conclusions: Our study provides mechanistic insight into how LHX2/FGF1 acts as a sufficient regulator pathway in NPC proliferation and metastasis, and the FGF1/FGFR1/2 trapping may contribute to the development of a novel target for NPC therapy.

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FGF1 and IGF1-conditioned 3D culture system promoted the amplification and cancer stemness of lung cancer cells

Cited by 35 publications

References 72 publications

LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY

LINE-1 Retrotransposition Promotes the Development and Progression of Lung Squamous Cell Carcinoma by Disrupting the Tumor-Suppressor Gene FGGY

Lung CSC‐derived exosomal miR‐210‐3p contributes to a pro‐metastatic phenotype in lung cancer by targeting FGFRL1

LHX2 facilitates the progression of nasopharyngeal carcinoma via activating the autocrine secretion of FGF1

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