MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells

Yang, Ting; He, Wanming; Cui, Fei; Xia, Jianbo; Zhou, Rui; Wu, Zhenzhen; Zhao, Yang; Shi, Min

doi:10.18632/oncotarget.7634

Cited by 37 publications

(28 citation statements)

References 26 publications

(32 reference statements)

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“…Additionally, M3R functional inhibition by small interference RNA also contributed to apoptosis and restrained cell invasion/migration in gastric cancer36. Song et al .…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

Xiao

Tang

et al. 2017

Sci Rep

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Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation. Moreover, ACh, via M3R, activated the EGFR signaling to induce the phosphorylation of ERK1/2 and AKT, and blocking EGFR pathway by specific inhibitor AG1478 suppressed the ACh induced cell proliferation. Furthermore, the M3R antagonist 4-DAMP and darifenacin could markedly inhibit gastric tumor formation in vivo. 4-DAMP could also significantly enhance the cytotoxic activity of 5-Fu against the MKN45 and BGC823 cells, and induce the expression of apoptosis-related proteins such as Bax and Caspase-3. Together, these findings indicated that the autocrine ACh could act through M3R and the EGFR signaling to promote gastric cancer cells proliferation, targeting M3R or EGFR may provide us a potential therapeutic strategy for gastric cancer treatment.

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“…Additionally, M3R functional inhibition by small interference RNA also contributed to apoptosis and restrained cell invasion/migration in gastric cancer36. Song et al .…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

Xiao

Tang

et al. 2017

Sci Rep

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“…MACC1 promotes human gastric cancer cell proliferation and invasion [10–12], and is overexpressed in diverse human malignancies, including BC [13–16]. A previous study associated MACC1 polymorphisms with HER2-positive BC patient clinical outcome, suggesting that MACC1 is a potential BC biomarker [17].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic value of serum MACC1 in breast cancer patients

Tan

Xie²,

et al. 2016

Oncotarget

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Metastasis-associated in colon cancer-1 (MACC1) promotes colorectal cancer progression and predicts prognosis. The aim of our study was to determine the diagnostic and prognostic value of preoperative serum MACC1 levels in breast cancer patients. Serum MACC1 levels were measured in 378 breast cancer patients, 120 patients with benign breast disease, and 40 healthy volunteers using an ELISA. Serum MACC1 levels were higher in breast cancer patients than patients with benign disease or healthy volunteers. Increased serum MACC1 was associated with breast cancer TNM stage (P < 0.001), tumor size (P < 0.001), lymph node metastasis (P < 0.001), and Ki-67 status (P = 0.014). Serum MACC1 measurement successfully discriminated breast cancer patients from normal and healthy controls (AUC = 0.785, 95% CI: 0.746–0.825) with an optimal cut-off value of 38.35 pg/ml (sensitivity = 0.725, specificity = 0.696). Moreover, serum MACC1 exhibited significant prognostic value in breast cancer (AUC = 0.757, 95% CI: 0.700–0.814), and high MACC1 was associated with poor disease-free survival (HR 5.63, 95% CI: 3.51–9.04; P < 0.001). Our findings demonstrated that circulating MACC1 could serve as a reliable diagnostic and prognostic biomarker for breast cancer.

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“…However, we also showed the contribution of the nicotinic-dependent pathways in this effect. This is a particularly important finding since, while the implication of muscarinic receptors in gastric carcinogenesis has been highlighted by several studies, [4][5][6]23,24 there are much less data on the potential role of nicotinic receptors in this process. Indeed, the association between GC and tobacco smoking has been demonstrated by epidemiological studies and meta-analyses showing an increased risk of GC in smokers as compared to nonsmokers with a relative risk of about 1.6 and a doseresponse relationship.…”

Section: Discussionmentioning

confidence: 98%

Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type

et al. 2018

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Gastric cancer is the third leading cause of cancer-related death worldwide, but the mechanisms of gastric carcinogenesis are not completely understood. Recently, the role of cholinergic neuronal pathways in promoting this process has been demonstrated. Our aim was to extend these studies and to evaluate, using an in vitro model of tumorspheres, the effect of acetylcholine on human gastric cancer cells, and the role of acetylcholine receptors and of the nitric oxide pathway, in this effect. The gastric cancer cell line MKN-45 of the diffuse type of gastric cancer was cultured in the presence of acetylcholine, or different agonists or inhibitors of muscarinic and nicotinic acetylcholine receptors, or nitric oxide donor or inhibitor of the nitric oxide pathway, and the number and size of tumorspheres were assessed. The expression of cancer stem cell markers (CD44 and aldehyde dehydrogenase) was also evaluated by immunofluorescence and quantitative reverse transcription polymerase chain reaction. We showed that acetylcholine increased both the number and size of tumorspheres and that this effect was reproduced with both muscarinic and nicotinic acetylcholine receptors agonists and was inhibited by both receptor antagonists. The nitric oxide donor stimulated the tumorsphere formation, while the nitric oxide synthesis inhibitor inhibited the stimulatory effect of acetylcholine. Moreover, acetylcholine increased the expression of stem cell markers on gastric cancer cells. These results indicate that acetylcholine induces the stem cell properties of gastric cancer cells and both muscarinic and nicotinic receptors and a nitrergic pathway might be involved in this effect.

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MACC1 mediates acetylcholine-induced invasion and migration by human gastric cancer cells

Cited by 37 publications

References 26 publications

Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

Diagnostic and prognostic value of serum MACC1 in breast cancer patients

Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type

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