The Metabolic Profile of Tumors Depends on Both the Responsible Genetic Lesion and Tissue Type

Yuneva, Mariia; Fan, Teresa W.‐M.; Allen, T. C.; Higashi, Richard M.; Ferraris, Dana; Tsukamoto, Takashi; Matés, José M.; Alonso, Francisco; Wang, Chunmei; Seo, Youngho; Chen, Xin; Bishop, J. Michael

doi:10.1016/j.cmet.2011.12.015

Cited by 576 publications

(582 citation statements)

References 57 publications

(79 reference statements)

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“…In support of this view, tumours with the same driving mutations exhibit different metabolic profiles depending on their tissue microenvironment [70].…”

Section: Regulation Of Cancer Cell Metabolismmentioning

confidence: 66%

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Andersen

Moreira

Pedersen

2014

Phil. Trans. R. Soc. B

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Major changes in intra-and extracellular pH homoeostasis are shared features of most solid tumours. These changes stem in large part from the metabolic shift of most cancer cells towards glycolytic metabolism and other processes associated with net acid production. In combination with oncogenic signalling and impact from factors in the tumour microenvironment, this upregulates acid-extruding plasma membrane transport proteins which maintain intracellular pH normal or even more alkaline compared with that of normal cells, while in turn acidifying the external microenvironment. Mounting evidence strongly indicates that this contributes significantly to cancer development by favouring e.g. cancer cell migration, invasion and chemotherapy resistance. Finally, while still under-explored, it seems likely that non-cancer cells in the tumour microenvironment also exhibit altered pH regulation and that this may contribute to their malignant properties. Thus, the physical tumour microenvironment and the cancer and stromal cells within it undergo important reciprocal interactions which modulate the tumour pH profile, in turn severely impacting on the course of cancer progression. Here, we summarize recent knowledge of tumour metabolism and the tumour microenvironment, placing it in the context of tumour pH regulation, and discuss how interfering with these properties may be exploited clinically.

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“…In support of this view, tumours with the same driving mutations exhibit different metabolic profiles depending on their tissue microenvironment [70].…”

Section: Regulation Of Cancer Cell Metabolismmentioning

confidence: 66%

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Andersen

Moreira

Pedersen

2014

Phil. Trans. R. Soc. B

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“…Given the ge netic and meta bolic het ero gene ity of can cers, proper pa tient strat i fi ca tion will be re quired ac cord ing to the meta bolic sta tus of their tu mors in or der to de sign ro bust clin i cal tri als and to ul ti mately tai lor treat ments tar get ing me tab o lism [273,274], even though it is emerg ing that dif fer ent can cers con verge their me tab o lism along side tu mor pro gres sion [198]. Nev er the less, a sys tem atic un der stand ing of how ac ti vated onco genes specif i cally in flu ence me tab o lism, es pe cially in re la tion ship to the tis sue of ori gin [267], will be es sen tial for the suc cess of fu ture clin i cal tri als.…”

Section: Discussionmentioning

confidence: 99%

“…Al though stud ies on cell cul tures showed that mi to chon dr ial res pi ra tion is lim ited in sev eral can cer cell lines [262][263][264], in vivo data showed that mi to chon dr ial oxy gen con sump tion is not im paired in tu mors and that ox ida tive glu cose me tab o lism is re quired for tu mor growth [265]. The dis crep ancy be tween in vitro and in vivo ob ser va tions pleads for the use of spon ta neously aris ing tu mor mod els, which in te grate dri ver mu ta tions, the tu mor mi croen vi ron ment and the sur round ing 3D tis sue ar chi tec ture [253,266,267]. In a re cent study [253], au thors char ac ter ized glu t a mine me tab o lism in ge net i cally en gi neered mouse mod els of lung can cer.…”

Section: Metabolic Differences Between In Vitro and In Vivo Models Ofmentioning

confidence: 99%

Cancer metabolism in space and time: Beyond the Warburg effect

Danhier

Bański

Payen

et al. 2017

Biochimica et Biophysica Acta (BBA) - Bioenergetics

177

139

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Available online xxx Keywords:Can cer Me tab o lism Mi to chon dria Het ero gene ity Metas ta sis A B S T R A C T Al tered me tab o lism in can cer cells is piv otal for tu mor growth, most no tably by pro vid ing en ergy, re duc ing equiv a lents and build ing blocks while sev eral metabo lites ex ert a sig nal ing func tion pro mot ing tu mor growth and pro gres sion. A can cer tis sue can not be sim ply re duced to a bulk of pro lif er at ing cells. Tu mors are in deed com plex and dy namic struc tures where sin gle cells can het ero ge neously per form var i ous bi o log i cal ac tiv i ties with dif fer ent meta bolic re quire ments. Be cause tu mors are com posed of dif fer ent types of cells with meta bolic ac tiv i ties af fected by dif fer ent spa tial and tem po ral con texts, it is im por tant to ad dress me tab o lism tak ing into ac count cel lu lar and bi o log i cal het ero gene ity. In this re view, we de scribe this het ero gene ity also in meta bolic fluxes, thus show ing the rel a tive con tri bu tion of dif fer ent meta bolic ac tiv i ties to tu mor pro gres sion ac cord ing to the cel lu lar con text. This ar ti cle is part of a Spe cial Is sue en ti tled Res pi ra tory com plex I, edited by Giuseppe Gas parre, Ro drigue Rossig nol and Pierre Son veaux. Abbreviations: ACL, ATP cit rate lyase; AMPK, adeno sine monophos phate ki nase; ARG1, L argi nine me tab o liz ing en zyme arginase 1; BCAA, branched chain amino acid; Bcl2, B cell lym phoma 2; CAF, can cer as so ci ated fi brob last; CIC, can cer ini ti at ing cell; COX2, cy tochrome ox i dase; CSC, can cer stem cell; CREB, cyclic adeno sine monophos phate re sponse el e ment bind ing pro tein; DEC1, dif fer en tially ex pressed in chon dro cytes 1; EMT, ep ithe lial to mes enchy mal tran si tion; FAK, fo cal ad he sion ki nase; FAS, fatty acid syn thase; FBP, fruc tose 1,6 bis pho s phate; FDG PET, [ F] flu o rodeoxyglu cose positron emis sion to mog ra phy; GAPDH, glyc er alde hyde 3 phos phate de hy dro ge nase; HIF 1, hy poxia ac ti vated fac tor 1; HK2, hex ok i nase 2; HMGB1, high mo bil ity group box 1; HU VEC, hu man um bil i cal vein en dothe lial cell; IFN γ, in ter feron gamma; LDH, lac tate de hy dro ge nase; MEF, murine em bry onic fi brob last; MET, mes enchy mal to ep ithe lial tran si tion; MRI, mag netic res o nance imag ing; mTORC1, mam malian tar get of ra pamycin com plex 1; NSCLC, non small cell lung can cer; OX PHOS, ox ida tive phos pho ry la tion; PDAC, pan cre atic duc tal ade no car ci noma; PHD, pro lyl hy drox y lase; pHe, ex tra cel lu lar pH; pHi, in tra cel lu lar pH; PK, pyru vate ki nase; PPP, pen tose phos phate path way; REDD1, reg u lated in de vel op ment and DNA dam age re sponse 1; RhoA, Ras ho molog gene fam ily, mem ber A; ROS, re ac tive oxy gen species; SASP, senes cence as so ci ated se cre tory phe no type; SCO2, syn the sis of cy tochrome ox i dase 2; SGK 1, serum and glu co cor ti coid reg u lated ki nase 1 Sirt1, sir tuin 1; TAM, tu mor as so ci ated macrophage; TIGAR, TP53 in duced gly col y ...

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“…These data argue that tumors adapt the normal metabolic program of their tissue-oforigin to support inappropriate cell proliferation. In fact, expressing different oncogenes in the same tissue (MYC and MET in the liver) as well as the same oncogene in different tissues (MYC in liver and lung) had distinct effects on glucose and glutamine metabolism, suggesting that both oncogene and tissue type contribute to the metabolic phenotype of cancers (28).…”

Section: The Role Of Tissue-of-origin and Environment In Shaping Cancmentioning

confidence: 99%

Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

Mayers

Heiden

2017

Cancer Research

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Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy.

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The Metabolic Profile of Tumors Depends on Both the Responsible Genetic Lesion and Tissue Type

Cited by 576 publications

References 57 publications

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment

Cancer metabolism in space and time: Beyond the Warburg effect

Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

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