1. Academic Validation
  2. ANKFN1 plays both protumorigenic and metastatic roles in hepatocellular carcinoma

ANKFN1 plays both protumorigenic and metastatic roles in hepatocellular carcinoma

  • Oncogene. 2022 Jul;41(29):3680-3693. doi: 10.1038/s41388-022-02380-0.
Yanyan Wang  # 1 Yue Zhang  # 1 Jiaqi Mi  # 1 Chenchen Jiang  # 2 3 Qiang Wang 4 Xinwei Li 1 Menglin Zhao 1 Zhijun Geng 1 Xue Song 1 Jing Li 1 Lugen Zuo 1 Sitang Ge 1 Zining Zhang 1 Hexin Wen 1 Zishu Wang 5 Fang Su 6
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, PR China.
  • 2 Cancer Neurobiology Group, School of Biomedical Sciences & Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
  • 3 School of Medicine & Public Health, The University of Newcastle, Callaghan, NSW, 2308, Australia.
  • 4 Bengbu Medical College, Bengbu, 233004, Anhui, PR China.
  • 5 The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, PR China. wzshahbb@163.com.
  • 6 The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, PR China. sufang2899@163.com.
  • # Contributed equally.
Abstract

Ankyrin repeat and fibronectin type III domain containing 1 (ANKFN1) is reported to be involved in human height and developmental abnormalities, but the expression profile and molecular function of ANKFN1 in hepatocellular carcinoma (HCC) remain unknown. This study aimed to evaluate the clinical significance and biological function of ANKFN1 in HCC and investigate whether ANKFN1 can be used for differential diagnosis in HCC. Here, we showed that ANKFN1 was upregulated in 126 tumor tissues compared with adjacent nontumorous tissues in HCC patients. The upregulation of ANKFN1 in HCC was associated with cirrhosis, alpha-fetoprotein (AFP) levels and poor prognosis. Moreover, silencing ANKFN1 expression suppressed HCC cell proliferation, migration, invasion, and metastasis in vitro and subcutaneous tumorigenesis in vivo. However, ANKFN1 overexpression promoted HCC proliferation and metastasis in an orthotopic liver transplantation model and attenuated the above biological effects in HCC cells. ANKFN1 significantly affected HCC cell proliferation by inducing G1/S transition and cell Apoptosis. Mechanistically, we demonstrated that ANKFN1 promoted cell proliferation, migration, and invasion via activation of the cyclin D1/CDK4/CDK6 pathway by stimulating the MEK1/2-ERK1/2 pathway. Moreover, ANKFN1-induced cell proliferation, migration, and invasion were partially reversed by ERK1/2 inhibitors. Taken together, our results indicate that ANKFN1 promotes HCC cell proliferation and metastasis by activating the MEK1/2-ERK1/2 signaling pathway. Our work also suggests that ANKFN1 is a potential therapeutic target for HCC.

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