2. Academic Validation
  3. DCAF1 interacts with PARD3 to promote hepatocellular carcinoma progression and metastasis by activating the Akt signaling pathway

DCAF1 interacts with PARD3 to promote hepatocellular carcinoma progression and metastasis by activating the Akt signaling pathway

  • J Exp Clin Cancer Res. 2024 May 6;43(1):136. doi: 10.1186/s13046-024-03055-2.
Jinyao Zhang # 1,  Yuze Shi # 2,  Ke Ding # 3,  Weiwei Yu 4,  Jianbo He 2,  Beicheng Sun 5 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Graduate School, Nanjing, Jiangsu Province, 210008, China.
  • 2 Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, 210008, China.
  • 3 Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, 210008, China.
  • 4 Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, 210008, China.
  • 5 Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Peking Union Medical College Graduate School, Nanjing, Jiangsu Province, 210008, China. [email protected].
  • 6 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230022, China. [email protected].
  • # Contributed equally.
PMID: 38711082 DOI: 10.1186/s13046-024-03055-2
Abstract

Background: Hepatocellular carcinoma (HCC) is a fatal malignancy with poor prognosis due to lack of effective clinical interference. DCAF1 plays a vital role in regulating cell growth and proliferation, and is involved in the progression of various malignancies. However, the function of DCAF1 in HCC development and the underlying mechanism are still unknown. This study aimed to explore the effect of DCAF1 in HCC and the corresponding molecular mechanism.

Methods: Quantitative Real-Time PCR, Western blot and immunostaining were used to determine DCAF1 expression in tumor tissues and cell lines. Subsequently, in vitro and in vivo experiments were conducted to explore the function of DCAF1 in tumor growth and metastasis in HCC. Coimmunoprecipitation, mass spectrometry and RNA Sequencing were performed to identify the underlying molecular mechanisms.

Results: In this study, we found that DCAF1 was observably upregulated and associated with poor prognosis in HCC. Knockdown of DCAF1 inhibited tumor proliferation and metastasis and promoted tumor Apoptosis, whereas overexpressing DCAF1 yielded opposite effects. Mechanistically, DCAF1 could activate the Akt signaling pathway by binding to PARD3 and enhancing its expression. We also found that the combined application of DCAF1 knockdown and Akt Inhibitor could significantly suppress subcutaneous xenograft tumor growth.

Conclusions: Our study illustrates that DCAF1 plays a crucial role in HCC development and the DCAF1/PARD3/Akt axis presents a potentially effective therapeutic strategy for HCC.

Keywords

Akt; DCAF1; Hepatocellular carcinoma; PARD3.

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