2. Academic Validation
  3. ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner

ACTR5 controls CDKN2A and tumor progression in an INO80-independent manner

  • Sci Adv. 2022 Dec 23;8(51):eadc8911. doi: 10.1126/sciadv.adc8911.
Xiaobao Xu 1,  Anthony K N Chan 1,  Mingli Li 1,  Qiao Liu 1,  Nicole Mattson 1,  Sheela Pangeni Pokharel 1,  Wen-Han Chang 1,  Yate-Ching Yuan 2,  Jinhui Wang 2,  Roger E Moore 2,  Patrick Pirrotte 2 3,  Jun Wu 2,  Rui Su 1 2,  Markus Müschen 4,  Steven T Rosen 2,  Jianjun Chen 1 2,  Lu Yang 1,  Chun-Wei Chen 1 2
Affiliations

Affiliations

  • 1 Department of Systems Biology, Beckman Research Institute - City of Hope, Duarte, CA, USA.
  • 2 City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • 3 Cancer and Cell Biology Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.
  • 4 Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
PMID: 36563143 DOI: 10.1126/sciadv.adc8911
Abstract

Epigenetic dysregulation of cell cycle is a hallmark of tumorigenesis in multiple cancers, including hepatocellular carcinoma (HCC). Nonetheless, the epigenetic mechanisms underlying the aberrant cell cycle signaling and therapeutic response remain unclear. Here, we used an epigenetics-focused CRISPR interference screen and identified ACTR5 (actin-related protein 5), a component of the INO80 chromatin remodeling complex, to be essential for HCC tumor progression. Suppression of ACTR5 activated CDKN2A expression, ablated CDK/E2F-driven cell cycle signaling, and attenuated HCC tumor growth. Furthermore, high-density CRISPR gene tiling scans revealed a distinct HCC-specific usage of ACTR5 and its interacting partner IES6 compared to the Other INO80 complex members, suggesting an INO80-independent mechanism of ACTR5/IES6 in supporting the HCC proliferation. Last, our study revealed the synergism between ACTR5/IES6-targeting and pharmacological inhibition of CDK in treating HCC. These results indicate that the dynamic interplay between epigenetic regulators, tumor suppressors, and cell cycle machinery could provide novel opportunities for combinational HCC therapy.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15777
    99.94%, CDK4/6抑制剂
    CDK
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