Monoamine oxidase A suppresses hepatocellular carcinoma metastasis by inhibiting the adrenergic system and its transactivation of EGFR signaling

Li, Jun; Yang, Xiaomei; Wang, Yahui; Feng, Min; Liu, Xiaojin; Zhang, Yanli; Huang, Shuo; Wu, Zheng; Xue, Feng; Qin, Wenxin; Gu, Jianren; Xia, Qiang; Zhang, Zhigang

doi:10.1016/j.jhep.2014.02.025

Cited by 112 publications

(89 citation statements)

References 37 publications

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“…These findings suggest that MAOA might play a key role in mediating prostate cancer progression. However, Li et al demonstrated that MAOA expression was remarkably downregulated in clinical HCC tissue samples (31), and that MAOA suppressed HCC metastasis by inhibiting the adrenergic system and its transactivation of EGFR signaling (31). Huang et al also found that MAOA expression was inhibited by coordinated epigenetic and IL-6-driven events in human cholangiocarcinoma (32), and that overexpression of MAOA suppressed cholangiocarcinoma growth and invasion (32).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that prostate cancer and HCC exhibit completely different MAOA expression levels (24,31), and to date, MAOA expression has not been reported in NSCLC. To investigate the expressions of MAOA and EMT markers in NSCLC tissues, immunohistochemical staining was performed in 45 pairs of NSCLC and patient-matched non-tumor adjacent lung tissues.…”

Section: Expressions Of Maoa and Emt Markers In Nsclc And Matched Nonmentioning

confidence: 92%

“…The functions of MAOA have been extensively studied in the context of neurological disorders, including mental depression, aggressive behaviors, and Parkinson's disease (22,23). Recent studies have indicated the role of MAOA in the progression of prostate cancer (24)(25)(26)(27)(28)(29)(30), hepatocellular carcinoma (HCC) (31), and cholangiocarcinoma (32). High Gleason grade or poorly differentiated prostate cancer exhibited increased MAOA expression (24), and the increased MAOA promoted prostate cancer metastasis (25,26 (25).…”

Section: Introductionmentioning

confidence: 99%

“…These studies suggested that MAOA might promote the progression of prostate cancer by mediating EMT. However, conflicting results were reported for HCC (31) and cholangiocarcinoma (32). Therefore, the role of MAOA may vary across cancer types, and therefore, it is essential to further understand the function of MAOA in other cancers.…”

Section: Introductionmentioning

confidence: 99%

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Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

Liu

et al. 2017

Oncol Lett

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Abstract. Monoamine oxidase A (MAOA), a mitochondrial enzyme, is closely associated with neurological disorders. Recently, MAOA has been linked to the progression of prostate cancer, hepatocellular carcinoma, and cholangiocarcinoma. However, MAOA was reported to have different effects on the progression of these types of cancer, and the role of MAOA in non-small cell lung cancer (NSCLC) progression remains unclear. The present study determined the expression of MAOA and epithelial to mesenchymal transition (EMT) markers in 45 pairs of NSCLC and matched non-tumor adjacent lung tissues, and further analyzed the correlation between MAOA expression and the EMT or the development of clinicopathological features. The results demonstrated that protein and mRNA expression levels of MAOA in NSCLC tissues were higher than those observed in the matched non-tumor adjacent lung tissues. Furthermore, the increased MAOA expression in NSCLC tissues was positively correlated with N-cadherin (r=0.525, P=0.002), Slug (r=0.515, P=0.001), and Twist (r=0.448, P= 0.008) expressions, but negatively correlated with E-cadherin expression (r=-0.387, P=0.01). Additionally, the elevated MAOA expression in NSCLC tissues was associated with late stage NSCLC (Z=-2.596, P=0.029) and lymph node metastases (Z=-2.378, P= 0.020). These findings suggest that MAOA may have a role in promoting NSCLC progression by mediating EMT. IntroductionLung cancer, the leading cause of cancer-related deaths worldwide, is commonly divided into two categories, small cell lung cancer (SCLC) and non-SCLC (NSCLC), depending on its degree of differentiation and morphological characteristics (1,2). NSCLC accounts for ~80% of primary lung cancers, including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma (3). The 5-year survival rate of NSCLC is only 7% (4). Moreover, lymph nodes and distant organ metastasis are the main reasons leading to treatment failure in NSCLC patients with radical resection (5,6).Epithelial to mesenchymal transition (EMT), a reversible biological process, is characterized by the loss of epithelial cell junction proteins (E-cadherin, Zo-1) (7,8), the gain of mesenchymal markers (vimentin, N-cadherin) (9,10), and the activation of transcription factors (Snail1, Slug, ZEB1, Twist) (11-15). Accumulating evidence indicates that EMT enhances tumor invasion, distant metastasis, and chemotherapy resistance in NSCLC, underscoring the need for a comprehensive understanding of the EMT function in NSCLC progression (16)(17)(18)(19).Monoamine oxidase A (MAOA), a mitochondria-bound enzyme, catalyzes the oxidative deamination of dietary amines and monoamine neurotransmitters, such as serotonin, norepinephrine, and dopamine (20,21). The functions of MAOA have been extensively studied in the context of neurological disorders, including mental depression, aggressive behaviors, and Parkinson's disease (22,23

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Section: Discussionmentioning

confidence: 99%

Section: Expressions Of Maoa and Emt Markers In Nsclc And Matched Nonmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

Liu

et al. 2017

Oncol Lett

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“…The activation of EGFR also plays a key role in the process of cell intravasation, by which tumour cells metastasize into intratumoural vasculature and metastasize to remote target organs (10,37,38). We further investigated the role of TGF-α/EGFR in HCC cells under hypoxic conditions.…”

Section: The Cox-2/pge2 Axis Regulates Hif-2α Nuclear Translocation Vmentioning

confidence: 99%

COX-2/PGE2 Axis Regulates HIF2α Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment

Dong

Liu

Zhi

et al. 2018

Clinical Cancer Research

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Tumor hypoxia and hypoxia-related sorafenib resistance adversely affected the prognosis of HCC patients. Hypoxia-inducible factor (HIF) s are defined as the central transcriptional mediator of hypoxic response. Recent efforts have identified HIF-2α that has been involved in sorafenib resistance. However, the regulatory mechanisms of HIF-2α activity in HCC remain obscure. Here, using both in vitro and in vivo HCC models, we show that the cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) axis is a driver of HIF-2α expression and activity, which then promotes HCC growth, metastasis and angiogenesis. We further show that COX-2 specific inhibitors synergistically enhanced the antitumour activity of sorafenib treatment by regulating the HIF-2α level and activity. These observations support further clinical developments of COX-2-specific inhibitors for HCC treatment and particularly for enhancing the response to sorafenib treatment.Research.

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Near‐Infrared Photodynamic Chemiluminescent Probes for Cancer Therapy and Metastasis Detection

et al. 2023

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There is growing interest in the development of chemiluminescence (CL) probes for phototheranostics because of their minimized tissue autofluorescence. However, due to a lack of near‐infrared (NIR)‐absorbing chemiluminophores, current probes for NIR CL‐guided phototherapy are based on nanoparticles made up of multiple components. We report bright unimolecular chemiluminophores with NIR absorptions and emissions, long CL half‐lives and ideal photodynamic efficiency. One luminophore is modified into an activatable probe, DBPOL, with a turn‐on CL signal and photodynamic activity that are specific to a cancer biomarker. The highly sensitive DBPOL allows CL‐guided photodynamic therapy which completely inhibits tumor growth and lung metastasis in mouse models, and can be applied for noninvasive monitoring of lung metastasis. We provide molecular guidelines for NIR‐absorbing CL probes for imaging‐guided phototherapy.

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Monoamine oxidase A suppresses hepatocellular carcinoma metastasis by inhibiting the adrenergic system and its transactivation of EGFR signaling

Abstract: Taken together, the results of our study may provide insights into the application of MAOA as a novel predictor of clinical outcomes and indicate that increasing MAOA expression or enzyme activity may be a new approach that can be used for HCC treatment.

Cited by 112 publications

References 37 publications

Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

COX-2/PGE2 Axis Regulates HIF2α Activity to Promote Hepatocellular Carcinoma Hypoxic Response and Reduce the Sensitivity of Sorafenib Treatment

Near‐Infrared Photodynamic Chemiluminescent Probes for Cancer Therapy and Metastasis Detection

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