Induction of CCL2 by siMAML1 through upregulation of TweakR in melanoma cells.
Constitutive activation of Notch signaling was found in melanoma cells. Using siRNA specifically knocking down Notch co-activator MAML1 blocked Notch down stream transcriptional repressor Hey1 expression, significantly upregulated TweakR and CCL2 mRNA and protein expression in melanoma cell line M624. Exogenous Tweak stimulated high level CCL2 production in siMAML transfected M624 cells, which was critically dependent on Tweak-TweakR ligation. CCL2 produced by siMAML1 transfected M624 stimulated with exogenous Tweak was functional chemoattractant to activated monocytes. This study supports targeting Notch signaling using small siRNA in melanoma cells may increase immune cell recruitment and restore natural immune surveillance in tumor microenvironment.
Kang
Shijun
S
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. DrKang5@163.com
Yang
Chunlan
C
Luo
Rongcheng
R
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008545:Melanoma / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000276:immunology*; D000074050:TWEAK Receptor; D015534:Trans-Activators; D014157:Transcription Factors; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D018124:Receptors, Tumor Necrosis Factor; D012097:Repressor Proteins; D000074050:TWEAK Receptor; D015534:Trans-Activators; D014157:Transcription Factors; C111835:CCL2 protein, human; C405694:Hairy, HRT1 protein; C430872:MAML1 protein, human