Zingerone suppresses proliferation, invasion, and migration of hepatocellular carcinoma cells by the inhibition of MTDH-mediated PI3K/Akt pathway

Fang, Jian; Zhu, Huifen; Xu, Pengcheng; Jiang, Renya

doi:10.1080/10799893.2021.1988970

Cited by 6 publications

(6 citation statements)

References 43 publications

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“… 36 Another study found that MTDH can promote the proliferation, invasion, and migration of HCC by activating PI3K/AKT signaling pathway. 37 The findings support upregulation of MTDH leading to increased cell mobility and invasiveness of HCC cells. In conclusion, MTDH has an oncogenic role and may be an important biomarker in HCC with MVI.…”

Section: Biomarkers Related To MVImentioning

confidence: 53%

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Zhao¹,

Wang²,

Xia³

et al. 2023

J Clin Transl Hepatol

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Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

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Section: Biomarkers Related To MVImentioning

confidence: 53%

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Zhao¹,

Wang²,

Xia³

et al. 2023

J Clin Transl Hepatol

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“… 20 , 21 In addition, MTDH also plays a key role in the activation of multiple signaling pathways, including PI3K/Akt, NF-κB, and Wnt/β-catenin pathways. 22–24 Although functional research on MTDH is relatively complete, its underlying mechanisms remain unclear. Currently, research studies on the mechanisms of MTDH are mainly focused on the upstream regulatory factor of noncoding RNA of MTDH, such as lncRNA FAM83H-AS1, 25 circ-NOL10, 26 and miR-9-3p, 27 etc.…”

Section: Discussionmentioning

confidence: 99%

Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity

Xu,

Yang,

Yang

et al. 2024

Cancer Biology & Therapy

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Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.

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“…Our previous study demonstrated that MTDH inhibits mitochondrial apoptosis and induces BC resistance by activating the MTDH/NF‐κB (Yang et al., 2022) pathway in BC cells. MTDH plays a role in hepatocellular carcinoma metastasis modulation by activating MTDH‐mediated PI3K/AKT/GSK‐3β signaling pathways (Fang et al., 2022), and overexpression of MTDH increases the phosphorylation of AKT and GSK‐3β, enabling MTDH to regulate many downstream AKT factors essential for cell proliferation and survival (Lee et al., 2006). The AKT inhibitor (MK‐2206) is a potent, oral allosteric inhibitor of all AKT isoforms with antitumor activity (Yu et al., 2009).…”

Section: Introductionmentioning

confidence: 99%

“…It is also closely associated with chemotherapy resistance (Hu et al., 2009) and metastasis of BC with a poor prognosis (Qin et al., 2019). MTDH regulates two distinct signaling pathways involved in tumorigenesis and metastasis: the MTDH/nuclear factor‐kappaB (NF‐κB) (El‐Ashmawy et al., 2019; Yang et al., 2022) and phosphoinositide 3‐kinase (PI3K)/AKT (protein kinase B, PKB)/glycogen synthase kinase‐3beta (GSK‐3β) pathways (Fang et al., 2022; Tian et al., 2022). Our previous study demonstrated that MTDH inhibits mitochondrial apoptosis and induces BC resistance by activating the MTDH/NF‐κB (Yang et al., 2022) pathway in BC cells.…”

Section: Introductionmentioning

confidence: 99%

Metadherin inhibits chemosensitivity of triple‐negative breast cancer to paclitaxel via activation of AKT/GSK‐3β signaling pathway

Chang,

Jia,

et al. 2023

Chem Biol Drug Des

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Triple‐negative breast cancer (TNBC) has an aggressive clinical course, and paclitaxel (PTX)‐based chemotherapy remains the main therapeutic drug. Metadherin (MTDH) acts as an oncogene that regulates proliferation, invasion, metastasis, and chemoresistance. This study aimed to investigate whether TNBC chemosensitivity to PTX was related to the MTDH/AKT/glycogen synthase kinase‐3beta (GSK‐3β) pathway. Clinical baseline characteristics and immunohistochemistry (IHC) were used to evaluate the expression and prognosis of MTDH and AKT (protein kinase B, PKB) in TNBC patient samples. MTDH shRNA, MTDH overexpression vector, MK‐2206, and PTX intervention were used in cell models and mouse tumor‐bearing models. Afterwards, mRNA and protein levels were assessed using quantitative real‐time polymerase chain reaction and Western blot. Evaluate the level of tumor cell apoptosis and cell cycle using flow cytometry. Cell viability was detected using Cell Count Kit 8. The in vivo imaging system is used to analyze the growth of tumors. We found that higher expression of MTDH or AKT resulted in poorer disease‐free survival and a lower Miller–Payne grade. MTDH promotes cell proliferation and increases p‐AKT and p‐GSK‐3β expression in TNBC cells. Notably, suppression of AKT terminated MTDH overexpression‐induced cell proliferation and apoptosis. MTDH knockdown or the AKT inhibitor MK2206 reduced the p‐AKT and p‐GSK‐3β ratio, reduced cell viability and proliferation, increased cell apoptosis, and increased chemosensitivity to PTX. In vivo, xenograft tumors of an MTDH knockdown+MK2206 group treated with PTX were the smallest compared to other groups. In short, MTDH inhibits TNBC chemosensitivity to PTX by activating the AKT/GSK‐3β signaling pathway.

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Zingerone suppresses proliferation, invasion, and migration of hepatocellular carcinoma cells by the inhibition of MTDH-mediated PI3K/Akt pathway

Cited by 6 publications

References 43 publications

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity

Metadherin inhibits chemosensitivity of triple‐negative breast cancer to paclitaxel via activation of AKT/GSK‐3β signaling pathway

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