Demethylation-Induced Overexpression of Shc3 Drives c-Raf–Independent Activation of MEK/ERK in HCC

Liu, Yun; Zhang, Xinran; Yang, Baohong; Zhuang, Hao; Guo, Hua; Wang, Wen; Li, Yuan; Chen, Ruibing; Li, Yongmei; Zhang, Ning

doi:10.1158/0008-5472.can-17-2432

Cited by 37 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tyrosine kinase Src was discovered more than 30 years ago as a kinase that is involved in the crosstalk between many signaling pathways, including the integrin/FAK, Ras/Raf/MEK, PI3K/AKT, and IGF1/IGF1R pathways, and Src activation promotes cell proliferation, adhesion, invasion, migration, metastasis, and tumorigenesis [13]. Recently, Liu et al [14] reported that increased expression of Src potentiates ERK activation and reverses sorafenib resistance in HCC. Thus, inhibition of Src may provide a new strategy for drug combination studies for HCC treatment [15].…”

Section: Discussionmentioning

confidence: 99%

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Liao

Song

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

Background: Chemo-resistance in hepatocellular carcinoma (HCC) is a major problem, and acquired drug resistance prevents cancer therapies from achieving complete responses. Molecular targeting therapy presents an opportunity to impede tumor through combination or sequential therapy, while the accurate effect is vague. Methods: The efficacy of combinations between oxaliplatin and anti-cancer molecular targeting drugs was screened. Strangely, the combined chemotherapy with oxaliplatin and saracatinib induced significantly antagonistic effects. Then the antitumor effects of combined treatment with saracatinib and oxaliplatin were confirmed in wide type HCC as well as in saracatinib-and oxaliplatin-resistant HCC. RNA sequencing was used to explore the resistance mechanism, and the roles of ATP-binding cassette transporter G1 (ABCG1) and Wnt signaling in oxaliplatin resistance were confirmed. Results: Chemotherapy with oxaliplatin and saracatinib individually induced strong anti-HCC effects, while combined or sequential treatment of HCC cells with these two drugs exhibited reduced efficacy compared to treatment with the single drugs. And it was saracatinib treatment caused oxaliplatin resistance. RNA sequencing revealed 458 genes that were altered by treatment with saracatinib and oxaliplatin. Of these, the gene encoding ABCG1 and Wnt-associated genes were significantly upregulated. Upregulation of ABCG1 and oxaliplatin resistance were associated with activation of Wnt signaling. Interference with ABCG1 expression or inhibition of Wnt signaling resulted in reversal of the saracatinib-induced oxaliplatin resistance in HCC. Conclusions: These studies demonstrated that combined or sequential chemotherapy with oxaliplatin and saracatinib reduced antitumor efficacy, and this antagonism was attributed to the activation of Wnt signaling and upregulation of ABCG1 by saracatinib.

show abstract

Section: Discussionmentioning

confidence: 99%

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Liao

Song

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…ERK activation has been involved in the regulation of proliferation and EMT of HCC cells [ 14 , 37 , 38 ]. Recently, it has been reported that increased Shc3 expression results in activation of MEK/ERK in HCC independently of c-Raf [ 45 ]. Shc is signaling partner for integrins [ 46 – 48 ].…”

Section: Discussionmentioning

confidence: 99%

Periostin involved in the activated hepatic stellate cells-induced progression of residual hepatocellular carcinoma after sublethal heat treatment: its role and potential for therapeutic inhibition

Zhang

Lin

et al. 2018

J Transl Med

View full text Add to dashboard Cite

BackgroundIncomplete thermal ablation may induce invasiveness of hepatocellular carcinoma (HCC). Here, we investigated whether activated hepatic stellate cells (HSCs) would accelerate the progression of residual HCC after sublethal heat treatment, and thus sought to identify the potential targets.MethodsHepatocellular carcinoma cells were exposed to sublethal heat treatment and then cultured with the conditioned medium from activated HSCs (HSC-CM). The cell proliferation, migration, invasion and parameters of epithelial–mesenchymal transition (EMT) were analyzed. In vivo tumor progression of heat-treated residual HCC cells inoculated with activated HSCs was studied in nude mice.ResultsHSC-CM significantly enhanced the proliferation, motility, invasion, prominent EMT activation and decreased apoptosis of heat-exposed residual HCC cells. These increased malignant phenotypes were markedly attenuated by neutralizing periostin (POSTN) in HSC-CM. Furthermore, exogenous POSTN administration exerted the similar effects of HSC-CM on heat-treated residual HCC cells. POSTN induced the prominent activation of p52Shc and ERK1/2 via integrin β1 in heat-exposed residual HCC cells. Vitamin D analog calcipotriol blocked POSTN secretion from activated HSCs. Calcipotriol plus cisplatin significantly suppressed the activated HSCs-enhanced tumor progression of heat-treated residual HCC cells via the inhibited POSTN expression and the increased apoptosis.ConclusionsActivated HSCs promote the tumor progression of heat-treated residual HCC through the release of POSTN, which could be inhibited by calcipotriol. Calcipotriol plus cisplatin could be used to thwart the accelerated progression of residual HCC after suboptimal heat treatment.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1676-3) contains supplementary material, which is available to authorized users.

show abstract

“…TUBB3 is a key mechanism of drug resistance and TUBB3 expression shows predictive value for the prognosis in many cancers [45]. SHC3 regulates signal transduction, thereby stimulating hepatocellular carcinoma proliferation, migration, invasion, and epithelialto-mesenchymal transition (EMT) [46]. BMP5 activates multiple signaling pathways such as p38 MAPK signaling [47].…”

Section: Discussionmentioning

confidence: 99%

A new immune signature for survival prediction and immune checkpoint molecules in lung adenocarcinoma

et al. 2020

View full text Add to dashboard Cite

Background: Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer. The prognostic signature could be reliable to stratify LUAD patients according to risk, which helps the management of the systematic treatments. In this study, a systematic and reliable immune signature was performed to estimate the prognostic stratification in LUAD. Methods: The profiles of immune-related genes for patients with LUAD were used as one TCGA training set: n = 494, other validation set 1: n = 226 and validation set 2: n = 398. Univariate Cox survival analysis was used to identify the candidate immune-related genes from each cohort. Then, the immune signature was developed and validated in the training and validation sets. Results: In this study, functional analysis showed that immune-related genes involved in immune regulation and MAPK signaling pathway. A prognostic signature based on 10 immune-related genes was established in the training set and patients were divided into high-risk and low-risk groups. Our 10 immune-related gene signature was significantly related to worse survival, especially during early-stage tumors. Further stratification analyses revealed that this 10 immune-related gene signature was still an effective tool for predicting prognosis in smoking or nonsmoking patients, patients with KRAS mutation or KRAS wild-type, and patients with EGFR mutation or EGFR wild-type. Our signature was negatively correlated with B cell, CD4+ T cell, CD8+ T cell, neutrophil, dendritic cell (DC), and macrophage immune infiltration, and immune checkpoint molecules PD-1 and CTLA-4 (P < 0.05). Conclusions: These findings suggested that our signature was a promising biomarker for prognosis prediction and can facilitate the management of immunotherapy in LUAD.

show abstract

Demethylation-Induced Overexpression of Shc3 Drives c-Raf–Independent Activation of MEK/ERK in HCC

Cited by 37 publications

References 35 publications

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Periostin involved in the activated hepatic stellate cells-induced progression of residual hepatocellular carcinoma after sublethal heat treatment: its role and potential for therapeutic inhibition

A new immune signature for survival prediction and immune checkpoint molecules in lung adenocarcinoma

Contact Info

Product

Resources

About