A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment.
A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment.
复制标题
DOI：
10.3389/fonc.2022.962928
复制
发表时间：
2022
影响因子：
4.7
通讯作者：
Kong, Mei
中科院分区：
文献类型：
--
作者：
Hanse, Eric A. A.;Kong, Mei
关键词：
快速增殖的肿瘤细胞的矛盾之处在于它们消耗细胞外营养，这通常导致体内营养不良的微环境。更好地了解细胞响应代谢应激所表现出的适应机制将打开针对肿瘤极端营养微环境的新治疗窗口。谷氨酰胺是肿瘤核心中消耗最严重的氨基酸之一，在这里，我们深入了解谷氨酰胺及其下游副产物α-酮戊二酸（αKG）对传达营养环境信息的重要性。这种交流是细胞培养适应能力的关键。我们强调了当αKG浓度在癌症中改变时所带来的表观遗传变化，并讨论了剥夺细胞的谷氨酰胺如何导致癌细胞去分化以及在外来环境中生长和茁壮成长的能力。当我们饿死细胞时，它们会适应生存。这些生存“技能”使他们能够出去寻找其他地方居住和转移。我们进一步研究了目前在实验室中模拟代谢肿瘤微环境的挑战，并讨论了考虑目前研究结果以靶向肿瘤营养不良微环境的策略。
A paradox of fast-proliferating tumor cells is that they deplete extracellular nutrients that often results in a nutrient poor microenvironment in vivo. Having a better understanding of the adaptation mechanisms cells exhibit in response to metabolic stress will open new therapeutic windows targeting the tumor’s extreme nutrient microenvironment. Glutamine is one of the most depleted amino acids in the tumor core and here, we provide insight into how important glutamine and its downstream by-product, α-ketoglutarate (αKG), are to communicating information about the nutrient environment. This communication is key in the cell’s ability to foster adaptation. We highlight the epigenetic changes brought on when αKG concentrations are altered in cancer and discuss how depriving cells of glutamine may lead to cancer cell de-differentiation and the ability to grow and thrive in foreign environments. When we starve cells, they adapt to survive. Those survival “skills” allow them to go out looking for other places to live and metastasize. We further examine current challenges to modelling the metabolic tumor microenvironment in the laboratory and discuss strategies that consider current findings to target the tumor’s poor nutrient microenvironment.
登录
查看更多内容
影响因子：
64.5
作者：
Ho PC;Bihuniak JD;Macintyre AN;Staron M;Liu X;Amezquita R;Tsui YC;Cui G;Micevic G;Perales JC;Kleinstein SH;Abel ED;Insogna KL;Feske S;Locasale JW;Bosenberg MW;Rathmell JC;Kaech SM
通讯作者：
Kaech SM
影响因子：
29
作者：
Best, Sarah A.;Gubser, Patrick M.;Sutherland, Kate D.
通讯作者：
Sutherland, Kate D.
影响因子：
29
作者：
Hwang, In-Young;Kwak, Sojung;Youn, Hong-Duk
通讯作者：
Youn, Hong-Duk
影响因子：
64.5
作者：
Faubert B;Li KY;Cai L;Hensley CT;Kim J;Zacharias LG;Yang C;Do QN;Doucette S;Burguete D;Li H;Huet G;Yuan Q;Wigal T;Butt Y;Ni M;Torrealba J;Oliver D;Lenkinski RE;Malloy CR;Wachsmann JW;Young JD;Kernstine K;DeBerardinis RJ
通讯作者：
DeBerardinis RJ
影响因子：
11.2
作者：
Dermadi, Denis;Valo, Satu;Nystrom, Minna
通讯作者：
Nystrom, Minna