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Nature Cancer reveals the phase separation mechanism of RIOK1, cracking the puzzle of drug resistance in liver cancer
02 Mar,2026
In the field of hepatocellular carcinoma (HCC), a globally prevalent malignant tumor, scientists have been tirelessly exploring new treatment strategies and targets. Recently, Professor Liu Lianxin's team from the First Affiliated Hospital of China University of Science and Technology (Anhui Provincial Hospital) published a research paper titled "RIOK1 phase separation restricts PTEN translation via stress granules activating tumor growth in hepatocellular carcinoma" in Nature Cancer (IF 23.5), a top-tier journal in cancer research, marking a new breakthrough in the field of HCC treatment. This study reveals the crucial role of RIOK1 protein in the stress adaptability regulation of HCC, and through the mechanism of liquid-liquid phase separation (LLPS), it elucidates the specific mechanisms by which RIOK1 promotes HCC progression and targeted drug resistance. Additionally, a potential combination strategy to enhance HCC treatment sensitivity is discovered, bringing new treatment hope to HCC patients [1]. Notably, the Shimadzu Imaging Mass Cytometry Microscope iMScope QT provided powerful spatial metabolomic data support in simulating the stress microenvironment with low glutamine levels within liver tumors.
In-depth analysis of the liquid-liquid phase separation (LLPS) mechanism
Through a series of biochemical experiments, the research team revealed how RIOK1 interacts with IGF2BP1 and G3BP1 proteins via the LLPS mechanism, promoting the assembly of stress granules (SGs). This, in turn, hijacks and inhibits the translation of PTEN mRNA, reduces the expression of PTEN protein, and subsequently promotes malignant proliferation and invasion of liver cancer cells.
Discovery of novel anticancer drugs
Based on the crucial role of RIOK1 in the progression of liver cancer, the research team screened and identified a marketed drug named chidamide, which can effectively downregulate the expression of RIOK1 and significantly enhance the anticancer effect of tyrosine kinase inhibitors (TKIs), providing new treatment options for patients with liver cancer.
02 Mar,2026
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