Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1

Jin, Haojie; Wang, Cun; Jin, Guang‐Zhi; Ruan, Haoyu; Gu, Danan; Wei, Lin; Wang, Hui; Wang, Ning; Arunachalam, Einthavy; Zhang, Yurong; Deng, Xuan; Chen, Yang; Xiong, Yi; Feng, Hugang; Yao, Ming; Fang, Jing‐Yuan; Gu, Jianren; Cong, Wen-ming; Qin, Wenxin

doi:10.1053/j.gastro.2017.05.045

Cited by 71 publications

(64 citation statements)

References 48 publications

(63 reference statements)

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“…1b). This result was also validated in our own dataset which we submitted previously (GSE84402) [28], and COL4A1 was upregulated in 11 of 14 HCC samples (Additional file3: Figure S1B). In another 89 pairs of HCC and adjacent normal tissues, COL4A1 was upregulated in 79 of 89 HCC samples (88.7%) by qRT-PCR analysis ( Fig.…”

Section: Col4a1 Is Upregulated In Hccsupporting

confidence: 81%

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

Wang

Jin

et al. 2020

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Background: Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood. Methods: In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as its most significantly differential expression. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Relationship between COL4A1 expression and clinicopathological parameters was also analyzed. Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression. Results: COL4A1 is the most significantly overexpressed collagen gene in HCC and it closely correlates with clinical stage. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor. Conclusion: COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.

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Section: Col4a1 Is Upregulated In Hccsupporting

confidence: 81%

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

Wang

Jin

et al. 2020

Preprint

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“…1b). This result was also validated in our own dataset which we submitted previously (GSE84402) [37], and COL4A1 was upregulated in 11 of 14 HCC samples (Additional le4: Figure S1B). In another 89 pairs of HCC and adjacent normal tissues, COL4A1 was upregulated in 79 of 89 HCC samples (88.7%) by qRT-PCR analysis ( Fig.…”

Section: Col4a1 Is Upregulated In Hccsupporting

confidence: 82%

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

Wang

Jin

et al. 2020

Preprint

Self Cite

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Background: Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood. Methods: In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression.Results: COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor. Conclusion: COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.

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“…NFAT1 functions as an integrator of multiple signaling pathways, which regulates genes central to many developmental systems and inflammatory responses (6,7). Abnormal activation of NFAT1 has been recognized in several malignant tumors, including breast cancer (36)(37)(38), colon carcinoma (37), lung cancer (39), esophageal carcinoma (40), hepatocellular carcinoma (41), and GBMs (12), which consistently promotes tumor cell motility and invasion. In these tumors, NFAT1 upregulates the expression of proinflammatory oncogenic genes (including MMPs and interleukins; refs.…”

Section: Discussionmentioning

confidence: 99%

NFAT1-Mediated Regulation of NDEL1 Promotes Growth and Invasion of Glioma Stem-like Cells

et al. 2019

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Glioma stem-like cells (GSC) promote tumor generation and progression. However, the mechanism of GSC induction or maintenance is largely unknown. We previously demonstrated that the calcium-responsive transcription factor nuclear factor of activated T cells-1 (NFAT1) is activated in glioblastomas and regulates the invasion of tumor cells. In this study, we further explored the role of NFAT1 in GSC. We found that NFAT1 expression was associated with an aggressive phenotype and predicted poor survival in gliomas. Compared with normal glioma cells, NFAT1 was upregulated in GSC. NFAT1 knockdown reduced GSC viability, invasion, and self-renewal in vitro and inhibited tumorigenesis in vivo, whereas NFAT1 overexpression enhanced the growth and invasion of GSCs. RNA sequencing showed that NFAT1 depletion was associated with reduced neurodevelopment protein 1-like 1 (NDEL1, a potential downstream target of NFAT1) expression, whereas NFAT1 overexpression induced NDEL1 expression. In addition, NFAT1 regulated the promoter activities of NDEL1, whereas rescue of NDEL1 in NFAT1-silenced GSC partially restored tumor growth and invasion. Upregulation of NFAT1-NDEL1 signaling elevated Erk activation, increased protein levels of stemness markers in GSC, and resulted in dedifferentiation of normal neuronal cells and astrocytes. Our results indicate that NFAT1 controls the growth and invasion of GSC partially through regulation of NDEL1. Targeting the NFAT1-NDEL1 axis therefore might be of potential benefit in the treatment of patients with glioma.Significance: NFAT1 controls the growth and invasion of GSCs, partially by regulating NDEL1. Targeting the NFAT1-NDEL1 axis might provide opportunities in treating patients with glioma. Immunofluorescence staining of NFAT1 in LN229, G10, and T98G GSCs. DAPI was used for nuclear staining. Scale bar, 25 mm. Results are presented as the mean AE SEM of triplicate samples from three independent experiments. Ã , P < 0.05; ÃÃ , P < 0.01.

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Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1

Cited by 71 publications

References 48 publications

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling

NFAT1-Mediated Regulation of NDEL1 Promotes Growth and Invasion of Glioma Stem-like Cells

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