Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

Wu, Jason; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Yang, Li; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L.; Zhau, Haiyen E.; Shih, Jean C.; Chung, Leland W.K.

doi:10.1172/jci70982

Cited by 185 publications

(256 citation statements)

References 84 publications

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“…The data on the inhibition of tumor growth in a PCA xenograft model were confirmed by a research consortium from the US and China (Wu et al, 2014) showing that MAO-A knockdown in a mouse xenograft model significantly reduced tumor growth but also disengaged the downstream signalling model of MAO-A driving hypoxia, oxidative stress and epithelial, mesenchymal transition [EMT], an important step whereby tumor cells acquire a more invasive and metastatic phenotype (Thiery, 2002). Additionally, the research team in the US generated a near-infrared labelled inhibitor of MAO-A based on the structure of clorgyline to study it in mouse PCa xenografts.…”

Section: Other Diseasesmentioning

confidence: 70%

“…Additionally, the research team in the US generated a near-infrared labelled inhibitor of MAO-A based on the structure of clorgyline to study it in mouse PCa xenografts. They demonstrated reduced expression of oncogenes Fos, Jun, NF-kB, and Myc and cell cycle regulators CCND1, CCNE1, and CDK4/6, along with increases in the levels of tumor suppressor gene TP53, cell cycle inhibitors CDKN1A and CDKN2A, and MAOA-downstream genes that promote EMT, tumor hypoxia, cancer cell migration, and invasion (Wu et al, 2014(Wu et al, , 2015. These data warrant further investigation of RIMAs in the treatment of prostate cancer.…”

Section: Other Diseasesmentioning

confidence: 85%

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Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Entzeroth¹,

Ratty²

2017

OJD

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Over more than 60 years, monoamine oxidase (MAO) inhibitors are available for therapy of central nervous diseases. Although they have shown to be efficacious specifically in the treatment of major depressive disorders and treatment-resistant depression, they became less a therapeutic choice for the physicians mostly due to severe side effects, such as liver failure and hypertensive crisis associated specifically with the first generation of inhibitors. Nevertheless, this class of drugs is still being used for treatment specifically as more selective and reversible inhibitors became available and will provide clinicians with additional treatment options. The current review revisits monoamine oxidase inhibitors and their potential in the treatment of human diseases, such as anxiety, depression, mood and personality disorders, and pain and introduces current ideas and developments.

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Section: Other Diseasesmentioning

confidence: 70%

Section: Other Diseasesmentioning

confidence: 85%

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Entzeroth¹,

Ratty²

2017

OJD

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“…In addition, elevated MAO‐A expression in prostate cancer cells was recently shown to promote metastasis by two distinct mechanisms—epithelial‐to‐mesenchymal transition and paracrine Shh signalling (Wu et al, 2014, 2017 ). These particular responses might depend on the cell type and on the amount of H 2 O 2 , which is known to drive dose‐dependent cellular effects (Duan, Duan, Zhang, & Tong, 2005; Giorgio et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Monoamine oxidase‐A is a novel driver of stress‐induced premature senescence through inhibition of parkin‐mediated mitophagy

et al. 2018

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Cellular senescence, the irreversible cell cycle arrest observed in somatic cells, is an important driver of age‐associated diseases. Mitochondria have been implicated in the process of senescence, primarily because they are both sources and targets of reactive oxygen species (ROS). In the heart, oxidative stress contributes to pathological cardiac ageing, but the mechanisms underlying ROS production are still not completely understood. The mitochondrial enzyme monoamine oxidase‐A (MAO‐A) is a relevant source of ROS in the heart through the formation of H2O2 derived from the degradation of its main substrates, norepinephrine (NE) and serotonin. However, the potential link between MAO‐A and senescence has not been previously investigated. Using cardiomyoblasts and primary cardiomyocytes, we demonstrate that chronic MAO‐A activation mediated by synthetic (tyramine) and physiological (NE) substrates induces ROS‐dependent DNA damage response, activation of cyclin‐dependent kinase inhibitors p21cip, p16ink4a, and p15ink4b and typical features of senescence such as cell flattening and SA‐β‐gal activity. Moreover, we observe that ROS produced by MAO‐A lead to the accumulation of p53 in the cytosol where it inhibits parkin, an important regulator of mitophagy, resulting in mitochondrial dysfunction. Additionally, we show that the mTOR kinase contributes to mitophagy dysfunction by enhancing p53 cytoplasmic accumulation. Importantly, restoration of mitophagy, either by overexpression of parkin or inhibition of mTOR, prevents mitochondrial dysfunction and induction of senescence. Altogether, our data demonstrate a novel link between MAO‐A and senescence in cardiomyocytes and provides mechanistic insights into the potential role of MAO‐dependent oxidative stress in age‐related pathologies.

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“…However, conflicting results were reported across different types of cancer, including prostate cancer (24)(25)(26)(27)(28)(29)(30), HCC (31), and cholangiocarcinoma (32). MAOA was demonstrated as being highly expressed in high-grade aggressive prostate cancer, and capable of mediating prostate tumorigenesis and metastasis (24)(25)(26)(27). Recently, MAOA was reported as a novel decision maker in apoptosis and autophagy processes occurring within hormone refractory neuroendocrine prostate cancer cells (28).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

Cited by 185 publications

References 84 publications

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

Monoamine oxidase‐A is a novel driver of stress‐induced premature senescence through inhibition of parkin‐mediated mitophagy

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

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