Delineating metabolic signatures of head and neck squamous cell carcinoma: phospholipase A2, a potential therapeutic target.
Delineating metabolic signatures of head and neck squamous cell carcinoma: phospholipase A2, a potential therapeutic target.
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DOI：
10.1016/j.biocel.2012.06.025
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发表时间：
2012-11
影响因子：
4
通讯作者：
Ramamoorthy, Ayyalusamy
中科院分区：
文献类型：
--
作者：
Tripathi, Pratima;Kamarajan, Pachiyappan;Somashekar, Bagganahalli S.;MacKinnon, Neil;Chinnaiyan, Arul M.;Kapila, Yvonne L.;Rajendiran, Thekkelnaycke M.;Ramamoorthy, Ayyalusamy
关键词：
深入了解头颈部鳞状细胞癌恶性转化的分子机制，对于开发新型高效的抗肿瘤药物具有重要意义。为了描述HNSCC的整体代谢，我们报告了来自上呼吸消化道不同部位（包括口底、舌和喉）的5名不同患者的HNSCC细胞的基于1H NMR的代谢谱。来自三个不同供体的正常人口腔角质形成细胞（NHOK）的原代培养物用于比较。使用细胞极性和非极性提取物的1H NMR光谱鉴定超过35种代谢产物。对NMR数据进行的主成分分析揭示了NHOK和HNSCC细胞的明确分类。HNSCC细胞表现出各种代谢物水平的显著改变，清楚地揭示了多种代谢事件的失调，包括瓦尔堡效应、氧化磷酸化、能量代谢、TCA循环回补通量、氨甲酰基分解、己糖胺途径、β-调节和抗氧化机制。此外，在HNSCC细胞中观察到的磷脂酰胆碱/溶血磷脂酰胆碱和磷酸胆碱/甘油磷酸胆碱的比率的显著改变以及花生四烯酸的升高揭示了改变的膜胆碱磷脂代谢（MCPM）。此外，在所有HNSCC细胞中观察到的磷脂酶A2（PLA 2），特别是胞质PLA 2（cPLA 2）的活性显著增加证实了改变的MCPM。总之，代谢组学的研究结果可以进一步阐明导致HNSCC的生物学方面，也提供了一个合理的基础，监测化疗的分子机制。cPLA 2可能成为HNSCC抗肿瘤治疗的潜在靶点。
A better understanding of molecular pathways involved in malignant transformation of head and neck squamous cell carcinoma (HNSCC) is essential for the development of novel and efficient anti-cancer drugs. To delineate the global metabolism of HNSCC, we report 1H NMR-based metabolic profiling of HNSCC cells from five different patients that were derived from various sites of the upper aerodigestive tract, including the floor of mouth, tongue and larynx. Primary cultures of normal human oral keratinocytes (NHOK) from three different donors were used for comparison. 1H NMR spectra of polar and non-polar extracts of cells were used to identify more than thirty-five metabolites. Principal component analysis performed on the NMR data revealed a clear classification of NHOK and HNSCC cells. HNSCC cells exhibited significantly altered levels of various metabolites that clearly revealed dysregulation in multiple metabolic events, including Warburg effect, oxidative phosphorylation, energy metabolism, TCA cycle anaplerotic flux, glutaminolysis, hexosamine pathway, osmo-regulatory and anti-oxidant mechanism. In addition, significant alterations in the ratios of phosphatidylcholine/lysophosphatidylcholine and phosphocholine/glycerophosphocholine, and elevated arachidonic acid observed in HNSCC cells reveal an altered membrane choline phospholipid metabolism (MCPM). Furthermore, significantly increased activity of phospholipase A2 (PLA2), particularly cytosolic PLA2 (cPLA2) observed in all the HNSCC cells confirm an altered MCPM. In summary, the metabolomic findings presented here can be useful to further elucidate the biological aspects that lead to HNSCC, and also provide a rational basis for monitoring molecular mechanisms in response to chemotherapy. Moreover, cPLA2 may serve as a potential therapeutic target for anti-cancer therapy of HNSCC.
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影响因子：
11.2
作者：
Dang CV
通讯作者：
Dang CV
影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
影响因子：
4.3
作者：
Dang, Chi V.
通讯作者：
Dang, Chi V.
影响因子：
8.8
作者：
Ferretti, A;D'Ascenzo, S;Podo, F
通讯作者：
Podo, F
影响因子：
6.2
作者：
Alhazzazi, Turki Y.;Kamarajan, Pachiyappan;Joo, Nam;Huang, Jing-Yi;Verdin, Eric;D'Silva, Nisha J.;Kapila, Yvonne L.
通讯作者：
Kapila, Yvonne L.