Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells

Pan, Lianhong; Feng, Fan; Wu, Jiaqin; Fan, Shibing; Han, Juanjuan; Wang, Shunxi; Yang, Li; Liu, Wanqian; Wang, Chunli; Xu, Kang

doi:10.1016/j.phrs.2022.106270

Cited by 151 publications

(103 citation statements)

References 63 publications

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“…Drugs or radiotherapy could exert their effects on cells by changing the expression or protein levels of some genes. For example, demethylzeylasteral could increase the expression of apoptotic genes and reduce the expression of antiapoptotic genes in liver cancer stem cells [ 23 ]. In addition, radiation treatment can promote the radiation resistance of colon cancer stem cells through the activation of JAK2/STAT3/CCND2 signaling pathway [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase CHIP Inhibits the Interaction between Hsp90β and MAST1 to Repress Radiation Resistance in Non-Small-Cell Lung Cancer Stem Cells

Tan

Zhang

Wang

et al. 2022

Stem Cells International

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The radiation resistance of cancer stem cells poses a critical obstacle for management of non-small-cell lung cancer (NSCLC). It is interesting to note that E3 ubiquitin ligase CHIP is involved in radiation resistance and stemness phenotypes in NSCLC, while the downstream mechanisms remain elusive. Therefore, this study is aimed at exploring the possible molecular mechanism of E3 ubiquitin ligase CHIP in radiation resistance of NSCLC stem cells. Cancer and adjacent normal tissues of NSCLC patients were collected to determine expression of CHIP, Hsp90β, and MAST1. CD133+ cells were isolated from the NSCLC tissues and the lung cancer cell line A549 by flow cytometric sorting. Accordingly, downregulated CHIP and upregulated Hsp90β and MAST1 were observed in cancer tissues from NSCLC patients and in NSCLC stem cells. Sphere formation assay, colony formation assay, and flow cytometry were performed to examine self-renewal ability, survival, and apoptosis of NSCLC stem cells. An animal model of tumor xenograft was developed in nude mice to observe the tumorigenic ability and radiation resistance of NSCLC stem cells. CHIP overexpression was demonstrated to inhibit the NSCLC stem cell properties and radiation resistance in vitro and in vivo. Mechanistically, CHIP promoted MAST1 ubiquitination by blocking Hsp90β interaction with MAST1, thus inhibiting MAST1 protein stability. Furthermore, CHIP-mediated downregulation of MAST1 protein stability inhibited the NSCLC stem cell properties and radiation resistance. Collectively, CHIP promotes the ubiquitination of MAST1 by blocking the interaction of Hsp90β with MAST1, leading to decreased MAST1 protein stability, which suppressed NSCLC stem cell properties and radiation resistance.

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Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase CHIP Inhibits the Interaction between Hsp90β and MAST1 to Repress Radiation Resistance in Non-Small-Cell Lung Cancer Stem Cells

Tan

Zhang

Wang

et al. 2022

Stem Cells International

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“…The optimal candidates for hepatic resection are patients with preserved hepatic function, Child-Pugh class A with normal bilirubin, and no portal hypertension. Otherwise, these patients have a high risk for HCC recurrence or liver failure (19)(20)(21)(22)(23). For the cases treated with systemic therapies, median survival has been only 1-1.5 years (19,(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients

Zhang

Feng²,

He³

et al. 2022

Front. Oncol.

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BackgroundOrthotopic liver transplantation (OLT) is a life-saving option for patients with hepatocellular carcinoma (HCC), but the expanded OLT criteria remain controversial.ObjectiveThe study aimed to explore whether expanded OLT criteria can be applied to Chinese cirrhotic patients with HCC.MethodsThis retrospective study analyzed risk factors for HCC recurrence and death and compared patients’ tumor characteristics and outcomes in groups of Milan, “Up-to-seven,” and Hangzhou criteria, and groups between met and unmet the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL.ResultsAmong 153 patients who underwent OLT for HCC from January 2015 to February 2019 in 4 years of follow-up, 20 (13.1%) patients had HCC recurrence, and 11 (7.2%) had HCC-related death. Multivariate Cox regression analysis showed that preoperative alpha-fetoprotein (AFP) of > 1000 ng/mL (hazard ratio [HR]: 10.05, 95% confidence interval [CI]: 2.45–41.13, P = 0.001) was an independent risk factor for HCC recurrence and HCC-related death (HR: 6.63, 95%CI: 1.31–33.52, P = 0.022). Patients who did not meet Milan criteria but satisfied the “Up-to-seven” criteria had no differences in overall survival (OS) (P = 0.69) and disease-free survival (DFS) (P = 0.35) than patients who met the Milan criteria. The combination of “Up-to-seven” criteria and AFP of < 1000 ng/mL differed significantly (HR: 18.9; 95% CI: 4.0–89.2; P < 0.001). Patients with HCC who met the “Up-to-seven” criteria and AFP of < 1000 ng/mL (n = 121) had excellent survival with 4-year OS of 91.6% (P < 0.001) and DFS of 90.8% (P < 0.001), which is significantly better compared to the other group (n = 32) (OS of 67.5% and DFS of 46.5%) and patients who met the Milan criteria (n = 108, OS of 89.8%, DFS of 89.6%), allowing 28.9% (13/45) of patients who did not meet the Milan criteria to benefit from OLT.ConclusionChinese cirrhotic patients with HCC who met the combinative criteria of “Up-to-seven” and AFP of < 1000 ng/mL had better survival than those who met the Milan criteria, and these combinative criteria benefited more patients and may become a better option for OLT.

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“… 40 Histone lactylation might occur separately from interleukin-6-induced inflammatory metabolic adaptation. 41 Thus, targeting lactylation may be a potential therapeutic approach for cancer, 42 inflammation, 38 Alzheimer's disease 43 and other brain disorders.…”

Section: Intersections In the Pathophysiological Changes Induced By T...mentioning

confidence: 99%

Rethinking the initial changes in subarachnoid haemorrhage: Focusing on real-time metabolism during early brain injury

Chen¹,

Galea²,

Macdonald³

et al. 2022

eBioMedicine

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Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells

Cited by 151 publications

References 63 publications

E3 Ubiquitin Ligase CHIP Inhibits the Interaction between Hsp90β and MAST1 to Repress Radiation Resistance in Non-Small-Cell Lung Cancer Stem Cells

E3 Ubiquitin Ligase CHIP Inhibits the Interaction between Hsp90β and MAST1 to Repress Radiation Resistance in Non-Small-Cell Lung Cancer Stem Cells

The Combination of AFP and “Up-To-Seven” Criteria May Be a Better Strategy for Liver Transplantation in Chinese Cirrhotic HCC Patients

Rethinking the initial changes in subarachnoid haemorrhage: Focusing on real-time metabolism during early brain injury

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