EGF promotes
            <i>DKK1</i>
            transcription in hepatocellular carcinoma by enhancing the phosphorylation and acetylation of histone H3

Niu, Jie; Li, Wei; Liang, Chao; Wang, Xiao; Yao, Xin; Yang, Ruo-Han; Zhang, Zhansheng; Liu, Han-Fang; Liu, Fan‐Ye; Pei, Shu-Hua; Sun, Hua; Fang, Dong; Xie, Songqiang

doi:10.1126/scisignal.abb5727

Cited by 32 publications

(25 citation statements)

References 55 publications

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“…Immunohistochemical staining was conducted as previously described (Niu et al, 2020). Briefly, tumors from the mice were dehydrated and embedded in paraffin after fixation with 4% paraformaldehyde.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

Zhang

Yang

Yao

et al. 2021

Cell Biology International

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Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8 + T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

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Section: Immunohistochemical Stainingmentioning

confidence: 99%

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

Zhang

Yang

Yao

et al. 2021

Cell Biology International

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“…In colon cancer SW480 cells, Genistein was found to affect histone H3 acetylation at the DKK1 promoter [ 69 ]. Additionally, Niu et al observed that epidermal growth factor (EGF) initiates DKK1 expression in HCC cells by increasing histone H3 acetylation through p300 [ 70 ] (Table 1 ). Together, these studies suggest that histone acetylation at the promoters of endogenous inhibitory molecules can promote expression of these gene to suppress Wnt/β-catenin signaling, which means that the deacetylation of histone at the promoters of these molecules is in favor of Wnt/β-catenin signaling.…”

Section: Introductionmentioning

confidence: 99%

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

You

Kong

et al. 2022

Cell Mol Biol Lett

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Canonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/β-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/β-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/β-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/β-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.

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“…DKK1 is a secretory Wnt antagonist, and abnormal expression of DKK1 has become recognized as an important regulator of many human cancers. Some reports indicate that DKK1 is a tumour promoter in pancreatic cancer, oesophageal cancer, and hepatocellular carcinoma [ 54 , 55 ]. In contrast, DKK1 expression is downregulated in thyroid cancer [ 56 ], cutaneous squamous cell carcinoma [ 57 ], and breast cancer [ 58 ], suggesting that DKK1 may have a tumour suppressive effect.…”

Section: Discussionmentioning

confidence: 99%

The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin

et al. 2022

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Background PolyC-RNA-binding protein 1 (PCBP1) functions as a tumour suppressor and RNA regulator that is downregulated in human cancers. Here, we aimed to reveal the biological function of PCBP1 in lung adenocarcinoma (LUAD). Methods First, PCBP1 was identified as an important biomarker that maintains LUAD through The Cancer Genome Atlas (TCGA) project screening and confirmed by immunohistochemistry and qPCR. Via colony formation, CCK8, IncuCyte cell proliferation, wound healing and Transwell assays, we confirmed that PCBP1 was closely related to the proliferation and migration of LUAD cells. The downstream gene DKK1 was discovered by RNA sequencing of PCBP1 knockdown cells. The underlying mechanisms were further investigated using western blot, qPCR, RIP, RNA pulldown and mRNA stability assays. Results We demonstrate that PCBP1 is downregulated in LUAD tumour tissues. The reduction in PCBP1 promotes the proliferation, migration and invasion of LUAD in vitro and in vivo. Mechanistically, the RNA-binding protein PCBP1 represses LUAD by stabilizing DKK1 mRNA. Subsequently, decreased expression of the DKK1 protein relieves the inhibitory effect on the Wnt/β-catenin signalling pathway. Taken together, these results show that PCBP1 acts as a tumour suppressor gene, inhibiting the tumorigenesis of LUAD. Conclusions We found that PCBP1 inhibits LUAD development by upregulating DKK1 to inactivate the Wnt/β-catenin pathway. Our findings highlight the potential of PCBP1 as a promising therapeutic target.

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EGF promotes DKK1 transcription in hepatocellular carcinoma by enhancing the phosphorylation and acetylation of histone H3

Cited by 32 publications

References 55 publications

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin

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