Metabolomics uncovers a link between inositol metabolism and osteosarcoma metastasis.
Metabolomics uncovers a link between inositol metabolism and osteosarcoma metastasis.
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DOI：
10.18632/oncotarget.15872
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发表时间：
2017-06-13
期刊：
影响因子：
--
通讯作者：
Khanna C
中科院分区：
文献类型：
--
作者：
Ren L;Hong ES;Mendoza A;Issaq S;Tran Hoang C;Lizardo M;LeBlanc A;Khanna C
癌症的发生和发展以复杂的分子事件为特征。这些事件的获得主要被认为是基因和蛋白质表达/功能改变的结果。最近的研究也表明代谢改变或“代谢重编程”的作用，也可能类似地促成这些事件。事实上，我们之前对骨肉瘤(OS)的研究发现，代谢变化与转移有关。基于这些发现，我们在这里试图建立一个更详细的了解代谢物或代谢途径的具体变化，这些变化可能导致观察到的与转移相关的代谢变化，由基因表达数据提示。这是使用高通量液体和基于气相色谱的质谱仪(LC/MS和GC/MS)的组合来进行的，以对四对高/低转移的OS细胞系进行全球代谢谱/差减。通过比较高转移细胞和低转移细胞代谢产物的同一性和水平，确定了几条差异激活的代谢途径，如精氨酸、谷胱甘肽、肌醇和脂肪酸代谢途径。为了进一步询问这些结果，我们通过将转移的OS细胞暴露于IP6(六磷酸肌醇)，研究了肌醇途径失调的影响。虽然IP6暴露对细胞增殖有轻微或极小的影响，但我们观察到细胞糖酵解减少，PI3K/Akt信号下调，并抑制OS转移进展。总的来说，这些数据支持在临床环境中进一步研究代谢敏感性作为抗转移策略，以及与转移进展相关的代谢组学改变的研究。
Cancer development and progression are characterized by complex molecular events. The acquisition of these events is primarily believed to result from alterations in gene and protein expression/function. Recent studies have also suggested the role of metabolic alterations, or “metabolic reprogramming,” that may similarly contribute to these events. Indeed, our previous investigations in osteosarcoma (OS) identified metabolic changes uniquely linked to metastasis. Based on those findings, here we sought to build a more detailed understanding of the specific alterations in metabolites or metabolic pathways that may be responsible for the observed metastasis-associated metabolic alterations, suggested by gene expression data. This was pursued using a combination of high-throughput liquid- and gas-chromatography-based mass spectrometry (LC/MS and GC/MS) for a global metabolic profiling/subtraction of four pairs of high/low metastatic OS cell lines. By comparing the identity and level of the metabolites between high/low metastatic cells, several metabolic pathways were identified to be differentially activated, such as arginine, glutathione, inositol and fatty acid metabolic pathways. To further interrogate these results, we investigated the effects of inositol pathway dysregulation, through the exposure of metastatic OS cells to IP6 (inositol hexaphosphate). Although IP6 exposures had modest to minimal effects on cell proliferation, we observed reduced cellular glycolysis, down-regulation of PI3K/Akt signaling and suppression of OS metastatic progression. Collectively these data supported further investigation of metabolic sensitivities as anti-metastatic strategies in a clinical setting as well as investigation of altered metabolomics associated with metastatic progression.
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在癌症转移中重新审视种子和土壤。
DOI：
10.1016/j.biocel.2009.01.015
发表时间：
2009-07
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Mendoza M;Khanna C
通讯作者：
Khanna C
影响因子：
4.1
作者：
Beger RD
通讯作者：
Beger RD
影响因子：
64.8
作者：
Sreekumar, Arun;Poisson, Laila M.;Rajendiran, Thekkelnaycke M.;Khan, Amjad P.;Cao, Qi;Yu, Jindan;Laxman, Bharathi;Mehra, Rohit;Lonigro, Robert J.;Li, Yong;Nyati, Mukesh K.;Ahsan, Aarif;Kalyana-Sundaram, Shanker;Han, Bo;Cao, Xuhong;Byun, Jaeman;Omenn, Gilbert S.;Ghosh, Debashis;Pennathur, Subramaniam;Alexander, Danny C.;Berger, Alvin;Shuster, Jeffrey R.;Wei, John T.;Varambally, Sooryanarayana;Beecher, Christopher;Chinnaiyan, Arul M.
通讯作者：
Chinnaiyan, Arul M.
影响因子：
11.2
作者：
Ren L;Hong SH;Chen QR;Briggs J;Cassavaugh J;Srinivasan S;Lizardo MM;Mendoza A;Xia AY;Avadhani N;Khan J;Khanna C
通讯作者：
Khanna C
影响因子：
15.9
作者：
Mendoza, Arnulfo;Hong, Sung-Hyeok;Khanna, Chand
通讯作者：
Khanna, Chand