Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines

Hussien, Rajaa; Brooks, George A.

doi:10.1152/physiolgenomics.00177.2010

Cited by 140 publications

(143 citation statements)

References 56 publications

(72 reference statements)

Supporting

Mentioning

129

Contrasting

Order By: Relevance

“…MCT1 was strongly expressed at plasma membrane in MDA-MB-468, Hs578T and BT20 (basal-like subtype cells), in accordance with our findings for human breast carcinoma samples (Pinheiro et al 2010). In MDA-MB-231, also basal-like subtype cells, MCT1 was not detected, as described by others (Asada et al 2003, Gallagher et al 2007, Hussien & Brooks 2011, and the same was observed for the Her2-positive subtype cell line (SkBr3). In contrast, MCT4 was strongly expressed at the plasma membrane in MDA-MB-231, as described by others (Hussien & Brooks 2011), as well as in SkBr3.…”

Section: Discussionsupporting

confidence: 92%

“…In MDA-MB-231, also basal-like subtype cells, MCT1 was not detected, as described by others (Asada et al 2003, Gallagher et al 2007, Hussien & Brooks 2011, and the same was observed for the Her2-positive subtype cell line (SkBr3). In contrast, MCT4 was strongly expressed at the plasma membrane in MDA-MB-231, as described by others (Hussien & Brooks 2011), as well as in SkBr3. Therefore, it seems that the plasma expression of these two isoforms is mutually exclusive in breast cancer, suggesting different mechanisms of regulation.…”

Section: Discussionsupporting

confidence: 83%

“…Importantly, we should not ignore the presence of intracellular expression of MCTs, especially MCT4. Actually, a recent study has shown mitochondrial expression of MCT2 and MCT4 in two breast cancer cell lines (MCF-7 and MDA-MB-231), indicating a role of MCTs in the mitochondria (Hussien & Brooks 2011). Additionally, two other studies have described a mitochondrial pyruvate carrier, which is a different protein from the MCTs (Bricker et al 2012, Herzig et al 2012.…”

Section: Discussionmentioning

confidence: 98%

See 2 more Smart Citations

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Morais-Santos¹,

Miranda-Gonçalves²,

Pinheiro³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

The tumour microenvironment is known to be acidic due to high glycolytic rates of tumour cells. Monocarboxylate transporters (MCTs) play a role in extracellular acidification, which is widely known to be involved in tumour progression. Recently, we have described the upregulation of MCT1 in breast carcinomas and its association with poor prognostic variables. Thus, we aimed to evaluate the effect of lactate transport inhibition in human breast cancer cell lines. The effects of a-cyano-4-hydroxycinnamate, quercetin and lonidamine on cell viability, metabolism, proliferation, apoptosis, migration and invasion were assessed in a panel of different breast cancer cell lines. MCT1, MCT4 and CD147 were differently expressed among the breast cancer cell lines and, as expected, different sensitivities were observed for the three inhibitors. Interestingly, in the most sensitive cell lines, lactate transport inhibition induced a decrease in cell proliferation, migration and invasion, as well as an increase in cell death. Results were validated by silencing MCT1 expression using siRNA. The results obtained here support targeting of lactate transport as a strategy to treat breast cancer, with a special emphasis on the basal-like subtype, which so far does not have a specific molecular therapy.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Morais-Santos¹,

Miranda-Gonçalves²,

Pinheiro³

et al. 2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…The ox ida tive path way of lac tate com prises lac tate up take in a process pri mar ily fa cil i tated by MCT1, a mono car boxy late trans porter with a high affin ity for lac tate [72], the con ver sion of lac tate and NAD to lac tate, NADH and H by lac tate de hy dro ge nase B (LDHB), and the mi to chon dr ial use of pyru vate [5] and NADH (im ported into mi to chon dria through the malate as par tate shut tle) [73]. Im por tantly, other au thors have re ported that LDHB can also re side in the mi to chon dria of some can cer cell lines, where they would gen er ate pyru vate and NADH from lac tate to di rectly fuel the TCA cy cle and the elec tron trans port chain, re spec tively [74,75]. The mi to chon dr ial lo cal iza tion of LDHB would be par tic u larly im por tant for gly colytic can cer cells that were re cently shown to use lac tate de rived from gly col y sis as a mi to chon dr ial re source to sup port lipid biosyn the sis [75].…”

Section: Metabolic Cooperation In Cancermentioning

confidence: 99%

Cancer metabolism in space and time: Beyond the Warburg effect

Danhier

Bański

Payen

et al. 2017

Biochimica et Biophysica Acta (BBA) - Bioenergetics

161

131

View full text Add to dashboard Cite

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 ...

show abstract

“…We have contributed several major publications (19,25,67,(82)(83)(84)(85)98), but additional experiments are required to evaluate the causative role of lactate on gene transcription, mitochondrial biogenesis, mitochondrial dynamics (MitoDyn), and mLOC protein turnover through redox-ROSCa ϩϩ homeostasis. The Warburg effect is a physiological response that is "hijacked" by cancer cells to support cell proliferation (170,210).…”

Section: Mitochondrial Dynamics In Skeletal Muscle and Other Lactate-mentioning

confidence: 99%

Exercise tames the wild side of the Myc network: a hypothesis

Gohil

Brooks

2012

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

Gohil K, Brooks GA. Exercise tames the wild side of the Myc network: a hypothesis. Am J Physiol Endocrinol Metab 303: E18 -E30, 2012. First published April 24, 2012; doi:10.1152/ajpendo.00027.2012We propose that the welldocumented therapeutic actions of repeated physical activities over human lifespan are mediated by the rapidly turning over proto-oncogenic Myc (myelocytomatosis) network of transcription factors. This transcription factor network is unique in utilizing promoter and epigenomic (acetylation/deacetylation, methylation/demethylation) mechanisms for controlling genes that include those encoding intermediary metabolism (the primary source of acetyl groups), mitochondrial functions and biogenesis, and coupling their expression with regulation of cell growth and proliferation. We further propose that remote functioning of the network occurs because there are two arms of this network, which consists of driver cells (e.g., working myocytes) that metabolize carbohydrates, fats, proteins, and oxygen and produce redox-modulating metabolites such as H 2O2, NAD ϩ , and lactate. The exercise-induced products represent autocrine, paracrine, or endocrine signals for target recipient cells (e.g., aortic endothelium, hepatocytes, and pancreatic ␤-cells) in which the metabolic signals are coupled with genomic networks and interorgan signaling is activated. And finally, we propose that lactate, the major metabolite released from working muscles and transported into recipient cells, links the two arms of the signaling pathway. Recently discovered contributions of the Myc network in stem cell development and maintenance further suggest that regular physical activity may prevent age-related diseases such as cardiovascular pathologies, cancers, diabetes, and neurological functions through prevention of stem cell dysfunctions and depletion with aging. Hence, regular physical activities may attenuate the various deleterious effects of the Myc network on health, the wild side of the Myc-network, through modulating transcription of genes associated with glucose and energy metabolism and maintain a healthy human status. myelocytomatosis; lactate shuttle; glycolysis; mitochondrial reticulum; mitochondrial biogenesis; mitochondrial dynamics; exertion; health; chronic diseases REGULAR PHYSICAL ACTIVITIES ameliorate or prevent numerous pathologies frequently associated with aging that include cardiovascular dysfunctions (103,183,200), diabetes (2,17,178,201,214), dementias (41), depression (86,195), and cancers (42, 165). Importantly, physical activity protects against some of these pathologies in a dose-dependent relationship (114,123,222), possibly through targeting the endothelium (173,208,212) that displays tissue-specific phenotypes (125,158,175,191). The molecular basis of this dose-dependent, regular, and "remote action" of skeletal muscle activity on functionally distinct organs needs clarification. In skeletal muscles, the initial and driving organ, transcriptional processes are activated by the exercise stimulus, which ...

show abstract

Mitochondrial and plasma membrane lactate transporter and lactate dehydrogenase isoform expression in breast cancer cell lines

Cited by 140 publications

References 56 publications

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Differential sensitivities to lactate transport inhibitors of breast cancer cell lines

Cancer metabolism in space and time: Beyond the Warburg effect

Exercise tames the wild side of the Myc network: a hypothesis

Contact Info

Product

Resources

About