Open Access

ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/β‑catenin signaling pathway

  • Authors:
    • Qi‑Feng Chen
    • Feng Shi
    • Tao Huang
    • Chaoyun Huang
    • Lujun Shen
    • Peihong Wu
    • Wang Li
  • View Affiliations

  • Published online on: July 24, 2020     https://doi.org/10.3892/or.2020.7704
  • Pages: 1425-1440
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Astrotactin 1 (ASTN1) is known to serve a physiological role in neuronal migration; however its role in liver cancer remains to be determined. In the present study, ASTN1 levels were lower in liver cancer tissues compared with those in matching normal tissue. ASTN1 levels were negatively associated with microscopic vascular invasion, advanced clinical stage and a less favorable prognosis in patients with hepatocellular carcinoma (HCC). Furthermore, ASTN1 overexpression in a liver cancer cell line reduced the migratory and invasive capacity of the cells. Based on bioinformatics analysis, ASTN1 levels were negatively associated with the Wnt signaling pathway. In addition, ASTN1 downregulated the protein expression levels of β‑catenin, T‑cell factor (TCF)1, TCF4, Jun proto‑oncogene (C‑jun), Myc proto‑oncogene (C‑myc), cyclooxygenase‑2 (COX2), metalloproteinase (MMP)2, MMP9 and vascular endothelial growth factor (VEGF) protein levels, indicative of suppression of Wnt signaling. Furthermore, XAV939‑induced Wnt signaling suppression reversed the ASTN1‑mediated inhibition of invasion and migration in cells. Overexpression of ASTN1 in xenografts reduced cancer development as well as Wnt signaling. TIMER analysis showed that ASTN1 expression was negatively correlated with B cell, macrophage and neutrophil infiltrating levels in HCC. Together, the results of the present study showed that ASTN1 reduced the migratory and invasive capacity of liver cancer cells, potentially served as a candidate biomarker for diagnosis and prediction of the prognosis of HCC, and was associated with immune infiltration. Understanding the underlying mechanisms of action of ASTN1 may facilitate the development of novel strategies for prevention and treatment of liver cancer.
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October-2020
Volume 44 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Chen QF, Shi F, Huang T, Huang C, Shen L, Wu P and Li W: ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/β‑catenin signaling pathway. Oncol Rep 44: 1425-1440, 2020
APA
Chen, Q., Shi, F., Huang, T., Huang, C., Shen, L., Wu, P., & Li, W. (2020). ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/β‑catenin signaling pathway. Oncology Reports, 44, 1425-1440. https://doi.org/10.3892/or.2020.7704
MLA
Chen, Q., Shi, F., Huang, T., Huang, C., Shen, L., Wu, P., Li, W."ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/β‑catenin signaling pathway". Oncology Reports 44.4 (2020): 1425-1440.
Chicago
Chen, Q., Shi, F., Huang, T., Huang, C., Shen, L., Wu, P., Li, W."ASTN1 is associated with immune infiltrates in hepatocellular carcinoma, and inhibits the migratory and invasive capacity of liver cancer via the Wnt/β‑catenin signaling pathway". Oncology Reports 44, no. 4 (2020): 1425-1440. https://doi.org/10.3892/or.2020.7704