scholarly journals The α9 Nicotinic Acetylcholine Receptor Mediates Nicotine-Induced PD-L1 Expression and Regulates Melanoma Cell Proliferation and Migration

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1991 ◽  
Author(s):  
Hai Duong Nguyen ◽  
You-Cheng Liao ◽  
Yuan-Soon Ho ◽  
Li-Ching Chen ◽  
Hui-Wen Chang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Nicotinic Acetylcholine ◽  
Cell Proliferation And Migration ◽  
Melanoma Cell Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Cigarette smoking is associated with an increased risk of melanoma metastasis. Smokers show higher PD-L1 expression and better responses to PD-1/PD-L1 inhibitors than nonsmokers. Here, we investigate whether nicotine, a primary constituent of tobacco, induces PD-L1 expression and promotes melanoma cell proliferation and migration, which is mediated by the α9 nicotinic acetylcholine receptor (α9-nAChR). α9-nAChR overexpression in melanoma using melanoma cell lines, human melanoma tissues, and assessment of publicly available databases. α9-nAChR expression was significantly correlated with PD-L1 expression, clinical stage, lymph node status, and overall survival (OS). Overexpressing or knocking down α9-nAChR in melanoma cells up- or downregulated PD-L1 expression, respectively, and affected melanoma cell proliferation and migration. Nicotine-induced α9-nAChR activity promoted melanoma cell proliferation through stimulation of the α9-nAChR-mediated AKT and ERK signaling pathways. In addition, nicotine-induced α9-nAchR activity promoted melanoma cell migration via activation of epithelial-mesenchymal transition (EMT). Moreover, PD-L1 expression was upregulated in melanoma cells after nicotine treatment via the transcription factor STAT3 binding to the PD-L1 promoter. These results highlight that nicotine-induced α9-nAChR activity promotes melanoma cell proliferation, migration, and PD-L1 upregulation. This study may reveal important insights into the mechanisms underlying nicotine-induced melanoma growth and metastasis through α9-nAChR-mediated carcinogenic signals and PD-L1 expression.

scholarly journals Mitochondrial Fatty Acid Oxidation Is Not Vital for Melanoma Cell Proliferation and Migration

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 314-314
Author(s):  
Marianne Collard ◽  
George Chen ◽  
Hyeon Jeong Lee ◽  
Zhicong Chen ◽  
Ji-Xen Cheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Fatty Acid ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Acid Oxidation ◽  
Cell Proliferation And Migration ◽  
Excess Adiposity ◽  
Melanoma Cell Proliferation ◽  
And Migration ◽  
Proliferation And Migration

Abstract Objectives Melanoma, the 5th most common cancer in the US, is the most aggressive form of skin cancer. Excess adiposity is associated with an increased risk of melanoma in males, and a high-fat diet promotes melanoma tumor growth in mice. Our group found that lipid droplet (LD) content increases with melanoma cell aggressiveness and that fatty acid uptake inhibition reduces cell proliferation and migration; however, the function of these lipids in melanoma is unknown. Since lipids can be used to produce energy by fatty acid oxidation (FAO), we sought to determine whether melanoma cells were using FAO to maintain aggressiveness. Methods Gene expression microarray was used to identify differences in gene expression, which was confirmed by RT-qPCR. WM983A, WM983B, 1205Lu and A375 human melanoma cells were treated with 5 µM Etomoxir and cell proliferation, migration, and respiration were quantified using the Quant-iT™ PicoGreen™ dsDNA Assay Kit, Boyden Chamber transwell migration, and Seahorse XFe96 Flux Analyzer, respectively. Results The most significantly altered genes expressed between four invasive, lipid-rich and four non-invasive, lipid-poor melanoma cells pertained to fatty acid metabolism. Carnitine palmitoyltransferase 1A (CPT1a), the rate limiting enzyme in mitochondrial FAO (mFAO), mRNA was increased in lipid-rich cells compared to the lipid-poor cells (p < 0.05, n = 6–7), indicating that melanoma cells may use LD lipids for mFAO. To determine the importance of mFAO to melanoma cells, we inhibited mFAO with etomoxir, an irreversible CPT1 inhibitor. Treatment of lipid-rich 1205Lu and A375 cells or lipid-poor WM983A and WM983B cells with etomoxir for 4 days had no effect on cell proliferation. Extracellular flux analysis of cells with or without etomoxir showed no difference in ATP production, indicating that melanoma cells do not use mFAO to generate energy under normal conditions. In motile cells, etomoxir reduced lipid-rich A375 cell migration by 8.8% (p = 0.05, n = 2). Conclusions Lipids play a role in melanoma aggressiveness; however, our results indicate that mFAO of lipids is not vital to melanoma cell proliferation or migration. Further studies are required to understand the implication of excess adiposity and circulating lipids in melanoma development and progression. Funding Sources Institutional Department Fund

scholarly journals Zerumbone inhibits melanoma cell proliferation and migration by altering mitochondrial functions

2017 ◽  
Vol 13 (4) ◽  
pp. 2397-2402 ◽  
Author(s):  
Hua Yan ◽  
Ming-Yuan Ren ◽  
Zheng-Xiang Wang ◽  
Shi-Jun Feng ◽  
Si Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Melanoma Cell ◽  
Cell Proliferation And Migration ◽  
Mitochondrial Functions ◽  
Melanoma Cell Proliferation ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Neurotrophins and Their Receptors Stimulate Melanoma Cell Proliferation and Migration

2008 ◽  
Vol 128 (8) ◽  
pp. 2031-2040 ◽  
Author(s):  
Francesca Truzzi ◽  
Alessandra Marconi ◽  
Roberta Lotti ◽  
Katiuscia Dallaglio ◽  
Lars E. French ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Melanoma Cell ◽  
Cell Proliferation And Migration ◽  
Melanoma Cell Proliferation ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Heterogeneity of Melanoma Cell Responses to Sleep Apnea-Derived Plasma Exosomes and to Intermittent Hypoxia

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4781
Author(s):  
Abdelnaby Khalyfa ◽  
Wojciech Trzepizur ◽  
Alex Gileles-Hillel ◽  
Zhuanhong Qiao ◽  
David Sanz-Rubio ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Intermittent Hypoxia ◽  
Melanoma Cells ◽  
Cell Proliferation And Migration ◽  
Exosomal Mirnas ◽  
And Migration ◽  
Melanoma Cell Lines ◽  
Proliferation And Migration

Obstructive sleep apnea (OSA) is associated with increased cutaneous melanoma incidence and adverse outcomes. Exosomes are secreted by most cells, and play a role in OSA-associated tumor progression and metastasis. We aimed to study the effects of plasma exosomes from OSA patients before and after adherent treatment with continuous positive airway pressure (CPAP) on melanoma cells lines, and also to identify exosomal miRNAs from melanoma cells exposed to intermittent hypoxia (IH) or normoxia. Plasma-derived exosomes were isolated from moderate-to-severe OSA patients before (V1) and after (V2) adherent CPAP treatment for one year. Exosomes were co-incubated with three3 different melanoma cell lines (CRL 1424; CRL 1619; CRL 1675) that are characterized by genotypes involving different mutations in BRAF, STK11, CDKN2A, and PTEN genes to assess the effect of exosomes on cell proliferation and migration, as well as on pAMK activity in the presence or absence of a chemical activator. Subsequently, CRL-1424 and CRL-1675 cells were exposed to intermittent hypoxia (IH) and normoxia, and exosomal miRNAs were identified followed by GO and KEG pathways and gene networks. The exosomes from these IH-exposed melanoma cells were also administered to THP1 macrophages to examine changes in M1 and M2 polarity markers. Plasma exosomes from V1 increased CRL-1424 melanoma cell proliferation and migration compared to V2, but not the other two cell lines. Exposure to CRL-1424 exosomes reduced pAMPK/tAMPK in V1 compared to V2, and treatment with AMPK activator reversed the effects. Unique exosomal miRNAs profiles were identified for CRL-1424 and CRL-1675 in IH compared to normoxia, with six miRNAs being regulated and several KEGG pathways were identified. Two M1 markers (CXCL10 and IL6) were significantly increased in monocytes when treated with exosomes from IH-exposed CRL-1424 and CRL-1625 cells. Our findings suggest that exosomes from untreated OSA patients increase CRL-1424 melanoma malignant properties, an effect that is not observed in two other melanoma cell lines. Exosomal cargo from CRL-1424 cells showed a unique miRNA signature compared to CRL-1675 cells after IH exposures, suggesting that melanoma cells are differentially susceptible to IH, even if they retain similar effects on immune cell polarity. It is postulated that mutations in STK-11 gene encoding for the serine/threonine kinase family that acts as a tumor suppressor may underlie susceptibility to IH-induced metabolic dysfunction, as illustrated by CRL-1424 cells.

The SDF-1/CXCR4 chemokine axis in uveal melanoma cell proliferation and migration

Tumor Biology ◽  
2015 ◽  
Vol 37 (3) ◽  
pp. 4175-4182 ◽  
Author(s):  
Jianjun Bi ◽  
Peng Li ◽  
Chuanyin Li ◽  
Jie He ◽  
Ying Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Uveal Melanoma ◽  
Melanoma Cell ◽  
Cell Proliferation And Migration ◽  
Uveal Melanoma Cell ◽  
Melanoma Cell Proliferation ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals LINC00470 accelerates the proliferation and metastasis of melanoma through promoting APEX1 expression

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ting Huang ◽  
Yong-Jie Wang ◽  
Mi-Tao Huang ◽  
Yu Guo ◽  
Li-Chang Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Underlying Mechanism ◽  
Melanoma Cells ◽  
Normal Tissues ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Functional Investigation ◽  
The Impact ◽  
Proliferation And Migration

AbstractRecently studies found that APEX1 was abnormally expressed in melanoma, indicating that it might be involved in the development of melanoma. However, the underlying mechanism and the interaction between APEX1 and LINC00470 in melanoma are not clear. Therefore, we aimed to investigate the role of LINC00470 in the development of melanoma in this work. We discovered that LINC00470 was overexpressed in melanoma tissues and cells compared with the adjacent normal tissues and cells by qPCR. The overexpression of LINC00470 promoted the proliferation and migration of melanoma cells. The functional investigation demonstrated that LINC00470 activated the transcription factor, ZNF131, to regulate the APEX1 expression, which finally promoted cell proliferation and migration. In contrast, knockdown of LINC00470 could significantly inhibit the melanoma cell proliferation and migration, and suppress the growth of tumor in vivo. Overexpression of APEX1 could reverse the impact of the silence of LINC00470 in melanoma cells. In summary, our studies revealed that LINC00470 promoted melanoma proliferation and migration by enhancing the expression of APEX1, which indicated that LINC00470 might be a therapeutic target for the treatment of melanoma.

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