MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Xu, Guohai; Ge, Yinggang; Xin, Tao; Gao, Qing; Liang, Xiaoyan

doi:10.3892/or.2017.5686

Cited by 9 publications

(12 citation statements)

References 41 publications

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“…For example, MARK1 is amplified in various cancer types, such as breast and liver cancer, and MARK2 is upregulated in lung cancer. However, these kinases have also been described as having tumor-suppressive effects 44 – 46 . MARK4 is reportedly upregulated in liver cancer, gliomas, and glioblastomas 47 , 48 ; however, the LKB1–MARK4 axis is reported to function as both an agonist and antagonist of Hippo signaling, suggesting cell-type dependent regulation of the LKB1–MARK4 axis 37 , 49 .…”

Section: Discussionmentioning

confidence: 99%

The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

Machino

Kaneko²,

Komatsu

et al. 2022

Commun Biol

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High-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.

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Section: Discussionmentioning

confidence: 99%

The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

Machino

Kaneko²,

Komatsu

et al. 2022

Commun Biol

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“…UC is the main risk factor inducing CC ( 124 ). In UC patients, CC risk is higher than the average population ( 125 , 126 ). The main feature of UC is the uncontrolled inflammation of the colon, causing acute abdominal pain, severe diarrhea, bloody stools, and reduced symptoms.…”

Section: Pos Regulates Nuclear Factor-kappa B (Nf-κb) Pathway mentioning

confidence: 93%

Pectin Oligosaccharides Ameliorate Colon Cancer by Regulating Oxidative Stress- and Inflammation-Activated Signaling Pathways

et al. 2018

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Colon cancer (CC) is the third common neoplasm worldwide, and it is still a big challenge for exploring new effective medicine for treating CC. Natural product promoting human health has become a hot topic and attracted many researchers recently. Pectin, a complex polysaccharide in plant cell wall, mainly consists of four major types of polysaccharides: homogalacturonan, xylogalacturonan, rhamnogalacturonan I and II, all of which can be degraded into various pectin oligosaccharides (POS) and may provide abundant resource for exploring potential anticancer drugs. POS have been regarded as a novel class of potential functional food with multiple health-promoting properties. POS have antibacterial activities against some aggressive and recurrent bacterial infection and exert beneficial immunomodulation for controlling CC risk. However, the molecular functional role of POS in the prevention of CC risk and progression remains doubtful. The review focuses on antioxidant and anti-inflammatory roles of POS for promoting human health by regulating some potential oxidative and inflammation-activated pathways, such as ATP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor-2 (Nrf2), and nuclear factor-κB (NF-κB) pathways. The activation of these signaling pathways increases the antioxidant and antiinflammatory activities, which will result in the apoptosis of CC cells or in the prevention of CC risk and progression. Thus, POS may inhibit CC development by affecting antioxidant and antiinflammatory signaling pathways AMPK, Nrf2, and NF-κB. However, POS also can activate signal transduction and transcriptional activator 1 and 3 signaling pathway, which will reduce antioxidant and anti-inflammatory properties and promote CC progression. Specific structural and structurally modified POS may be associated with their functions and should be deeply explored in the future. The present review paper lacks the important information for the linkage between the specific structure of POS and its function. To further explore the effects of prebiotic potential of POS and their derivatives on human immunomodulation in the prevention of CC, the specific POS with a certain degree of polymerization or purified polymers are highly demanded to be performed in clinical practice.

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“…MARK2 has been implicated in the development and progression of various cancer, including osteosarcoma, lung, and cervical cancer 10–13 . To explore the expression pattern of MARK2 in various tumorigenesis, we first analysed MARK2 expression in various cancer tissues using an oncomine database.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, MARK2 expression was associated with NF‐κB activity, DNA damage response, and cisplatin resistance in nonsmall cell lung cancer cells 12 . Moreover, a combination of baicalin with DDP synergistically inhibits lung cancer cell proliferation and invasion via downregulation of MARK2 and activation of Akt 13 . In contrast, MARK2 was shown to suppress the cell cycle progression and cell growth by activating AMPK, thereby preventing the mesenchymal‐like phenotype in cervical cancer cells 14 .…”

Section: Introductionmentioning

confidence: 99%

MARK2 potentiate aerobic glycolysis‐mediated cell growth in breast cancer through regulating mTOR/HIF‐1α and p53 pathways

Ponnusamy

Natarajan

Manoharan

2022

J of Cellular Biochemistry

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The microtubule‐affinity regulating kinases (MARKs) family plays a crucial role in regulating breast cancer development and progression. However, its precise function and the relevant molecular mechanism in breast cancer have not yet been elucidated. In this study, analysis of The Cancer Genome Atlas (TCGA) data revealed that MARK2 expression was markedly upregulated in breast cancer tissues, and high expression of MARK2 was correlated with poor survival. Functional assays showed that MARK2 deletion or inhibition suppressed aerobic glycolysis and cell growth as well as induced cell cycle arrest and apoptosis in breast cancer cells. Mechanistically, MARK2 stimulates mTOR‐mediated hypoxia‐inducible factor 1 alpha (HIF‐1α) transcription activity and represses p53‐transcription activity in breast cancer cells. TCGA data revealed that MARK2 expression was positively correlated with mTOR, Raptor, S6K1, glucose transporter 1, lactate dehydrogenase, HIF‐1α, and 4E‐BP1 expression, whereas negatively correlated with p53, p21, and Bax in breast cancer tissue. Conclusively, our study demonstrated that MARK2 promotes breast cancer aerobic glycolysis and cell proliferation, and inhibits apoptosis, in part, through regulating mTOR/HIF‐1α and p53 signaling pathways. Overall, these findings point to the potential of targeting MARK2 for breast cancer treatment.

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MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Cited by 9 publications

References 41 publications

The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

Pectin Oligosaccharides Ameliorate Colon Cancer by Regulating Oxidative Stress- and Inflammation-Activated Signaling Pathways

MARK2 potentiate aerobic glycolysis‐mediated cell growth in breast cancer through regulating mTOR/HIF‐1α and p53 pathways

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