Sperm-Specific Glycolysis Enzyme Glyceraldehyde-3-Phosphate Dehydrogenase Regulated by Transcription Factor SOX10 to Promote Uveal Melanoma Tumorigenesis.
Sperm-Specific Glycolysis Enzyme Glyceraldehyde-3-Phosphate Dehydrogenase Regulated by Transcription Factor SOX10 to Promote Uveal Melanoma Tumorigenesis.
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转录因子 SOX10 调控精子特异性糖酵解酶 3-磷酸甘油醛脱氢酶促进葡萄膜黑色素瘤发生
DOI：
10.3389/fcell.2021.610683
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发表时间：
2021
影响因子：
5.5
通讯作者：
Lin M
中科院分区：
文献类型：
--
作者：
Ding X;Wang L;Chen M;Wu Y;Ge S;Li J;Fan X;Lin M
黑色素瘤细胞表现出增加的有氧糖酵解，这代表了与恶性转化相关的主要生物化学改变;因此，糖酵解酶可用于在癌症治疗中选择性靶向癌细胞。精子特异性甘油醛-3-磷酸脱氢酶（GAPDHS）通过与NAD+还原为NADH偶联，将甘油醛-3-磷酸转化为1，3-二磷酸甘油酸。在这里，我们证明了GAPDHS在葡萄膜黑色素瘤（UM）中的表达显著高于正常对照。在功能上，UM细胞系中GAPDHS的敲低通过降低葡萄糖摄取、乳酸产生、三磷酸腺苷（ATP）产生、细胞生长和增殖来阻碍糖酵解;相反，GAPDHS的过表达促进糖酵解、细胞生长和增殖。此外，我们发现，SOX 10敲低减少了GAPDHS的激活，导致恶性表型减弱，而SOX 10过表达促进了GAPDHS的激活，导致恶性表型增强。SOX 10通过与GAPDHS启动子结合调节其表达而发挥其功能。重要的是，S 0X 10废除抑制体内肿瘤生长和增殖。总的来说，结果表明，受SOX 10调节的GAPDHS控制糖酵解并有助于UM肿瘤发生，突出了其作为治疗靶点的潜力。
Melanoma cells exhibit increased aerobic glycolysis, which represents a major biochemical alteration associated with malignant transformation; thus, glycolytic enzymes could be exploited to selectively target cancer cells in cancer therapy. Sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) switches glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by coupling with the reduction of NAD+ to NADH. Here, we demonstrated that GAPDHS displays significantly higher expression in uveal melanoma (UM) than in normal controls. Functionally, the knockdown of GAPDHS in UM cell lines hindered glycolysis by decreasing glucose uptake, lactate production, adenosine triphosphate (ATP) generation, cell growth and proliferation; conversely, overexpression of GAPDHS promoted glycolysis, cell growth and proliferation. Furthermore, we identified that SOX10 knockdown reduced the activation of GAPDHS, leading to an attenuated malignant phenotype, and that SOX10 overexpression promoted the activation of GAPDHS, leading to an enhanced malignant phenotype. Mechanistically, SOX10 exerted its function by binding to the promoter of GAPDHS to regulate its expression. Importantly, SOX10 abrogation suppressed in vivo tumor growth and proliferation. Collectively, the results reveal that GAPDHS, which is regulated by SOX10, controls glycolysis and contributes to UM tumorigenesis, highlighting its potential as a therapeutic target.
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影响因子：
5.3
作者：
Kuhlbrodt, K;Herbarth, B;Wegner, M
通讯作者：
Wegner, M
影响因子：
28.2
作者：
Parmenter TJ;Kleinschmidt M;Kinross KM;Bond ST;Li J;Kaadige MR;Rao A;Sheppard KE;Hugo W;Pupo GM;Pearson RB;McGee SL;Long GV;Scolyer RA;Rizos H;Lo RS;Cullinane C;Ayer DE;Ribas A;Johnstone RW;Hicks RJ;McArthur GA
通讯作者：
McArthur GA
影响因子：
1.8
作者：
Alghamdi SA;Zoroquiain P;Dias AB;Alhumaid SR;Aldrees S;Burnier MN Jr
通讯作者：
Burnier MN Jr
影响因子：
4.3
作者：
Hoek, Keith S.;Schlegel, Natalie C.;Steingrimsson, Eirikur
通讯作者：
Steingrimsson, Eirikur
DOI：
10.1016/s0006-291x(03)01222-1
发表时间：
2003-08-01
影响因子：
3.1
作者：
Arutyunova, EI;Danshina, PV;Muronetz, VI
通讯作者：
Muronetz, VI