ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance
Abstract
:1. Introduction
2. Cancer Stem Cells (CSCs)
3. ATP Binding Cassette (ABC) Transporter Structure and Location
4. Relevance of ABC Transporters in Cancer Cell Biology
5. ABC Transporter Regulation by Genes and Signalling Pathways
6. Endogenous Role of ABC Transporters in CSCs
7. ABC Transporters as Regulators of the Release of Active Biomolecules
8. ABC Transporters and Cellular Redox Status
9. ABC Transporters and Membrane Lipid Composition
10. ABC Transporters and Tumour Metabolism
11. ABC Transporters, Tumour Microenvironment and CSC Niche
12. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
ABC | ATP binding cassettes |
CSC | Cancer stem cells |
MDR | Multi drug resistance |
OCT4 | Octamer-binding transcription factor 4 |
ALDH | Aldehyde dehydrogenase |
EpCAM | Epithelial cell adhesion molecule |
EMT | Epithelial to mesenchymal transition |
SOX2 | Sex determining region y-box 2 |
MMIC | Malignant melanoma initiating cells |
P-gp | Permeability glycoprotein |
MRP | Multidrug resistance-associated protein |
BCRP | Breast cancer resistant protein |
APE | Aminoacyl tRNA-peptidyltRNA-decylated tRNA |
mTOR | Mammalian target of rapamycin |
PAK1 | p-21 Activated kinase 1 |
HMGA | High mobility group A |
EGFR | Epidermal growth factor receptor |
NF-κB | Nuclear factor kappa beta |
PI3K | Phosphoinositide 3-kinase |
COX2 | Cyclooxygenase 2 |
ERBB2 | Receptor tyrosine kinase 2 |
SMO | Smoothened |
PTEN | Phosphatase and tensin homolog |
DNAPK | DNA dependent protein kinase |
LMWH | Low molecular weight heparin |
HIF | Hypoxia inducible factor |
IL | Interleukin |
PG | Prostaglandin |
PGI2 | Prostacyclin |
LT | Leukotriene |
TX | Thromboxane |
LTC₄ | Leukotriene C 4 |
CXCR1 | C-X-C chemokine receptor type 1 |
CoA | Coenzyme A |
AMPK | AMP-activated protein kinase |
LPI | Lysophosphatidylinositol |
PDAC | Pancreatic ductal adenocarcinoma |
GPCR | G-protein-coupled receptor |
S1P | Sphingosine-1-phosphate |
GSH | Glutathione |
GSX | Glutathione conjugates |
GSSH | Glutathione disulphide |
HSC | Hematopoietic stem cells |
ROS | Reactive oxygen species |
MAPK | Mitogen activated protein kinase |
ERK | Extracellular signal-regulated kinase |
VEGF | Vascular endothelial growth factor |
PPARγ | Peroxisome proliferator-activated receptor |
MCT | Monocarbonate transporters |
ERK | Extracellular signal-regulated kinase |
ESC | Embryonic stem cells |
BBB | Blood brain barrier |
CNS | Central nervous system |
Nrf2 | Nuclear factor (erythroid-derived 2)-like 2 |
HDL | High density lipoproteins |
KRAS | Kirsten rat sarcoma |
MGMT | Ο6-methylguanine-DNA methyltransferase |
TCA | Tricarboxylic acid cycle |
TIS | Therapy induced senescence |
EC | Endothelial cells |
ECM | Extracellular matrix |
CAF | Cancer associated fibroblasts |
MSC | Mesenchymal stem cells |
TAM | Tumour associated macrophages |
GBM | Glioblastoma multiforme |
HNSCC | Head and neck squamous cell carcinoma |
EGF | Epidermal growth factor |
STAT3 | Signal transducer and activator of transcription factor 3 |
PKM2 | Pyruvate kinase M2 |
NK | Natural killer |
MIC | Metastasis initiating cells |
SETD | SET domain |
DTC | Disseminated tumour cells |
CTC | Circulating tumour cells |
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ABC Transporters | Tissue Localization | Expression in Cancer | Expression in Cancer Stem Cells (CSCs) | Regulation by Genes & Signaling Pathways | Exogenous Substrates | Endogenous Substrates |
---|---|---|---|---|---|---|
ABCA1 | Nervous and hematopoietic system as well as kidney, liver and the blood brain barrier [56] | Pancreas [57], serous ovarian cancer [56] | Serous ovarian cancer initiating cells [58] | Transforming growth factor-β (TGF-β) [59] NF-κB, P65 [60] | Cisplatin [58] | Phosphatidylcholine, phosphatidylserine and sphingomyelin [61] |
ABCA7 | Pancreas [57] | SREBP2 [62] | Phosphatidylserine [61], amyloid–β peptides [63,64] | |||
ABCB1/MDR1/P-gp | Small intestine, liver, kidney placenta, BBB [56] | Colorectal, liver, renal cancer [56] | Acute myeloid leukemia (AML) [65] glioblastoma [66,67,68] ovaries [54] breast [69] renal cell carcinoma [70] | P63, P73 [71], OCT4 [72], Mir43b [73], miR-27a [74] hsamiR-451 [75], receptor tyrosine kinase 2 (ERBB2) [69], SMO [76], CD133 and DNA-PK through the PI3K/Akt-NF-κB pathway [68], PKCγ [70], IL6, IL8, hypoxia [67,77] | Anthracyclines actinomycin D, colchicine, etoposide, teniposide, methotrexate, mitomycin C, mitoxantrone, paclitaxel, docetaxel, vincristine, vinblastine [78,79] | Steroids, lipids, bilirubin, bile acids, platelet activating factor [79] |
ABCB5 | CD133+ progenitor expressed in basal limbal epithelium among epidermal melanocytes [80] | Liver, lung, ovarian, thyroid [56] leukemia cells [81] | Malignant melanoma initiating cells (MMIC) [55,80,82] | Doxorubicin [83], 5-fluorouracil [84], camptothecin [84], irinotecan [84], mitozantrone [84], topotecan [84] | Interlukin 1 beta (IL1β) [82] | |
ABCC1/MRP1 | Lung, testes, peripheral blood monocellular cells [56] | Endometrial, glioma, head and neck, lymphoma, melanoma, renal, thyroid cancer [56] | Glioblastoma [67] | MYCN [85], OCT4 [72], miR-326 [86], hypoxia [67] | Methotrexate, edatrexate, ZD1694, doxorubicin, daunorubicin, epirubicin, idarubicin, etoposide, vincristine, vinblastine, paclitaxel, irinotecan, SN-38, flutamide, hydroxyflutamide [87,88] | Leukotriene C4 (LTC₄) [89], lysophosphatidylinositol (LPI) [44], sphingosine-1-phosphate (S1P) [90], glutathione (GSH), glutathione disulphide (GSSH) [88] |
ABCC3/MRP3 | Liver, intestine, colon, prostate, testes, brain, kidney [56] | Colorectal, cervical, lung, liver, thyroid, ovarian, pancreatic cancer [56] | OCT4 [72] | Cisplatin, doxorubicin, etoposide, methotrexate, teniopside, vincristine [88] | GSH [79] | |
ABCC4/MRP4 | Widely-expressed | Prostate, renal, head and neck, endometrial cancer [56] | Osteocarcinoma [91] | MYCN [85], OCT4 [72], PI3K [91] | Topotecan, PMEA, methotrexate, 6-mercaptopurin [88] | Prostaglandins (PGs), cyclic nucleotides, steroid, GSH conjugates and folate [92] |
ABCG2/BCRP | Placenta [93], intestine, liver, colon, breast [94] | Cervical, liver, lung, melanoma, testes, breast cancer [56] | Lung [49], pancreas [51,95], liver [96], breast [53,69], ovaries [50,97] | OCT4 [72], miR-212 [98], HMGA1 [97], ERBB2 [69], Hedgehog [99], SMO [76], PI3K/Akt [66] | Mitoxantrone, imatinib, anthracyclins, topotecan, flavopiridol, methotrexate [100] | Androgens [101], amyloid–β peptides [102], GSH [103] |
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Begicevic, R.-R.; Falasca, M. ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance. Int. J. Mol. Sci. 2017, 18, 2362. https://doi.org/10.3390/ijms18112362
Begicevic R-R, Falasca M. ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance. International Journal of Molecular Sciences. 2017; 18(11):2362. https://doi.org/10.3390/ijms18112362
Chicago/Turabian StyleBegicevic, Romana-Rea, and Marco Falasca. 2017. "ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance" International Journal of Molecular Sciences 18, no. 11: 2362. https://doi.org/10.3390/ijms18112362