ABCA1 inhibits PDGF-induced proliferation and migration of rat airway smooth muscle cell through blocking TLR2/NF-κB/NFATc1 signaling.
Cheng Wei,Yan Kun,Chen Yanni,Zhang Wen,Ji Zongzheng,Dang Chengxue
Journal of cellular biochemistry
Airway remodeling is a key feature of asthma, characterized by abnormal proliferation and migration of airway smooth muscle cells (ASMCs). ABCA1, a member of the ATP-binding cassette family of active transporters, plays an essential role in the progression of lung diseases. However, the contributions of ABCA1 in ASMCs remain to be explored. The purpose of the present study was to investigate the functional role and potential molecular mechanism of ABCA1 in platelet derived growth factor (PDGF)-induced primary rat ASMC proliferation and migration. We observed that PDGF- led to a significant decrease in the expression of ABCA1. Overexpression of ABCA1 strikingly suppressed PDGF-induced ASMC proliferation accompanied by a decrease in the expression of PCAN stimulated by PDGF. Additionally, augmentation of ABCA1 dramatically restrained PDGF-induced migration concomitant with attenuate the accumulation of MMP-2 and MMP-9 in response to PDGF. Furthermore, forced expression of ABCA1 enhanced contractile phenotype markers proteins including α-SMA along with sm-MHC, sm-α-actin, and calponin reduced by PDGF. Meanwhile, introduction of ABCA1 depressed ECM over-deposition induced by PDGF as reflected by a decrease in the expression of ECM protein collagen I and fibronectin. More importantly, addition of ABCA1 effectively suppressed the activity of TLR2/NF-κB signaling as well as diminished the expression of NFATc1 in rat ASMCs after PDGF stimulation. Interestingly, blockage of TLR2/NF-κB signaling effectively inhibited PDGF-induced proliferation and migration, these effects were similar to ABCA1. Taken together, these data implicated that ABCA1 suppressed PDGF-induced proliferation, migration, and contraction in rat ASMCs at least partly through TLR2/NF-κB/NFATc1 signaling, which might offer hope for the future treatment of airway remodeling in asthma.
10.1002/jcb.27046
E3317 promotes cholesterol efflux in macrophage cells via enhancing ABCA1 expression.
Wang Xiao,Luo Jinque,Li Ni,Liu Lunming,Han Xiaowan,Liu Chao,Zuo Xuan,Jiang Xinhai,Li Yining,Xu Yanni,Si Shuyi
Biochemical and biophysical research communications
Reverse cholesterol transport (RCT) plays an important role in cholesterol and lipid metabolism. Regulating the activities of key transporters and receptors in RCT, such as ATP-binding cassette transporter A1 (ABCA1), helps to prevent atherosclerotic cardiovascular disease. In this study, we used an ABCA1 promoter luciferase reporter assay to screen 20,000 compounds for ABCA1 upregulators. Compound E3317 (N-(6-butylbenzo[d]thiazol-2(3H)-ylidene)-3-(N-(2-cyanoethyl)sulfamoyl)benzamide)) was identified as a positive hit with an EC value of 0.2 μM in ABCA1p-LUC HepG2 cells. Thus, we hypothesized that E3317 might have cholesterol- and lipid metabolism-regulating effects through ABCA1 upregulation. E3317 significantly increased ABCA1 mRNA and protein expression in hepatic L02 cells and RAW264.7 macrophages. E3317 promoted cholesterol efflux to apolipoprotein A-I in RAW264.7 macrophages and significantly decreased lipid accumulation in oxidized low-density lipoprotein-induced murine RAW264.7 macrophages. Further studies using ABCA1 siRNA showed that the promotion of cholesterol efflux and decrease of lipid accumulation by E3317 depended on ABCA1 expression. Mechanistic studies indicated that E3317 regulated ABCA1 expression via activating nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays an important role in the regulation of glucose homeostasis and lipid metabolism. The structure of E3317 was docked in the ligand-binding domain of PPARγ (PBD code: 4EMA) to find the key binding amino acids. Site mutation assays confirmed that Y327 and F363 were the key PPARγ binding epitopes of E3317. Our results revealed that E3317 upregulates ABCA1 expression and thereby promotes cholesterol efflux. E3317 may regulate ABCA1 expression through PPARγ. Our findings provide a new compound, E3317, which may have beneficial cardiovascular effects.
10.1016/j.bbrc.2018.08.125
Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to α-tocopheryl succinate.
Prochazka Lubomir,Koudelka Stepan,Dong Lan-Feng,Stursa Jan,Goodwin Jacob,Neca Jiri,Slavik Josef,Ciganek Miroslav,Masek Josef,Kluckova Katarina,Nguyen Maria,Turanek Jaroslav,Neuzil Jiri
Apoptosis : an international journal on programmed cell death
α-Tocopheryl succinate (α-TOS) is a promising anti-cancer agent due to its selectivity for cancer cells. It is important to understand whether long-term exposure of tumour cells to the agent will render them resistant to the treatment. Exposure of the non-small cell lung carcinoma H1299 cells to escalating doses of α-TOS made them resistant to the agent due to the upregulation of the ABCA1 protein, which caused its efflux. Full susceptibility of the cells to α-TOS was restored by knocking down the ABCA1 protein. Similar resistance including ABCA1 gene upregulation was observed in the A549 lung cancer cells exposed to α-TOS. The resistance of the cells to α-TOS was overcome by its mitochondrially targeted analogue, MitoVES, that is taken up on the basis of the membrane potential, bypassing the enhanced expression of the ABCA1 protein. The in vitro results were replicated in mouse models of tumours derived from parental and resistant H1299 cells. We conclude that long-term exposure of cancer cells to α-TOS causes their resistance to the drug, which can be overcome by its mitochondrially targeted counterpart. This finding should be taken into consideration when planning clinical trials with vitamin E analogues.
10.1007/s10495-012-0795-1
High-density lipoprotein induces proliferation and migration of human prostate androgen-independent cancer cells by an ABCA1-dependent mechanism.
Sekine Yoshitaka,Demosky Steve J,Stonik John A,Furuya Yosuke,Koike Hidekazu,Suzuki Kazuhiro,Remaley Alan T
Molecular cancer research : MCR
Androgen deprivation therapy for prostate cancer leads to a significant increase of high-density lipoprotein (HDL), which is generally viewed as beneficial, particularly for cardiovascular disease, but the effect of HDL on prostate cancer is unknown. In this study, we investigated the effect of HDL on prostate cancer cell proliferation, migration, intracellular cholesterol levels, and the role of cholesterol transporters, namely ABCA1, ABCG1, and SR-BI in these processes. HDL induced cell proliferation and migration of the androgen-independent PC-3 and DU145 cells by a mechanism involving extracellular signal-regulated kinase (ERK) 1/2 and Akt, but had no effect on the androgen-dependent LNCaP cell, which did not express ABCA1 unlike the other cell lines. Treatment with HDL did not significantly alter the cholesterol content of the cell lines. Knockdown of ABCA1 but not ABCG1 or SR-BI by small interfering RNA (siRNA) inhibited HDL-induced cell proliferation, migration, and ERK1/2 and Akt signal transduction in PC-3 cells. Moreover, after treatment of LNCaP cells with charcoal-stripped fetal bovine serum, ABCA1 was induced ∼10-fold, enabling HDL to induce ERK1/2 activation, whereas small interfering RNA knockdown of ABCA1 inhibited HDL-induced ERK1/2 activation. Simvastatin, which inhibited ABCA1 expression in PC-3 and DU145 cells, attenuated HDL-induced PC-3 and DU145 cell proliferation, migration, and ERK1/2 and Akt phosphorylation. In human prostate biopsy samples, ABCA1 mRNA expression was ∼2-fold higher in the androgen deprivation therapy group than in subjects with benign prostatic hyperplasia or pretreatment prostate cancer groups. In summary, these results suggest that HDL by an ABCA1-dependent mechanism can mediate signal transduction, leading to increased proliferation and migration of prostate cancer cells.
10.1158/1541-7786.MCR-10-0008
Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1.
Lee Byron H,Taylor Margaret G,Robinet Peggy,Smith Jonathan D,Schweitzer Jessica,Sehayek Ephraim,Falzarano Sara M,Magi-Galluzzi Cristina,Klein Eric A,Ting Angela H
Cancer research
Recent epidemiologic data show that low serum cholesterol level as well as statin use is associated with a decreased risk of developing aggressive or advanced prostate cancer, suggesting a role for cholesterol in aggressive prostate cancer development. Intracellular cholesterol promotes prostate cancer progression as a substrate for de novo androgen synthesis and through regulation of AKT signaling. By conducting next-generation sequencing-based DNA methylome analysis, we have discovered marked hypermethylation at the promoter of the major cellular cholesterol efflux transporter, ABCA1, in LNCaP prostate cancer cells. ABCA1 promoter hypermethylation renders the promoter unresponsive to transactivation and leads to elevated cholesterol levels in LNCaP. ABCA1 promoter hypermethylation is enriched in intermediate- to high-grade prostate cancers and not detectable in benign prostate. Remarkably, ABCA1 downregulation is evident in all prostate cancers examined, and expression levels are inversely correlated with Gleason grade. Our results suggest that cancer-specific ABCA1 hypermethylation and loss of protein expression direct high intracellular cholesterol levels and hence contribute to an environment conducive to tumor progression.
10.1158/0008-5472.CAN-12-3128
Expression of the lipid transporters ABCA3 and ABCA1 is diminished in human breast cancer tissue.
Schimanski S,Wild P J,Treeck O,Horn F,Sigruener A,Rudolph C,Blaszyk H,Klinkhammer-Schalke M,Ortmann O,Hartmann A,Schmitz G
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
ATP-binding cassette transporters ABCA3 and ABCA1 are related to a differentiated, lipid-secreting phenotype of type II pneumocytes. Since mammary gland epithelial cells also show pronounced lipid metabolism and secretion, we investigated the expression of these proteins in normal as well as in neoplastic breast tissue. Normal human breast tissue, breast cancer cell lines, and 162 tumor samples of patients with primary unilateral invasive breast cancer were analyzed for ABCA3 and ABCA1 protein expression by immunohistochemistry using tissue microarrays. Strong ABCA3 and ABCA1 expression was found in the inner layer of normal mammary gland epithelium. Concurrent cytoplasmic ABCA3 and ABCA1 immunoreactivity was found in 9 of 11 breast cancer cell lines. ABCA3 and ABCA1 were shown to be differentially expressed in human breast cancer. Loss of ABCA3 staining was significantly associated with positive nodal status and negative progesterone receptor expression. In multivariate analysis, diminished ABCA3 expression proved to be a significant, independent and adverse risk factor for tumor recurrence. ABCA1 expression was associated with positive lymph nodes, but not significantly associated with tumor recurrence or breast cancer-specific survival. ABCA3 and ABCA1 are strongly expressed in normal mammary gland epithelium. Decreased ABCA3 expression in breast cancer seems to be associated with poor prognosis.
10.1055/s-0029-1241859
ABC-cassette transporter 1 (ABCA1) expression in epithelial cells in Chlamydia pneumoniae infection.
Korhonen Juha T,Olkkonen Vesa M,Lahesmaa Riitta,Puolakkainen Mirja
Microbial pathogenesis
ATP-binding cassette transporter A1 (ABCA1) mediates reverse cholesterol transport and innate immunity response in different cell types. We have investigated the regulation of ABCA1 expression in response to intracellular Chlamydia pneumoniae infection in A549 epithelial lung carcinoma cells. C. pneumoniae infection decreased ABCA1 expression in A549 cells, and the activity of the ABCA1 promoter was decreased. The decreased promoter activity was dependent on its E-box and GnT-box elements of the promoter. Chlamydial growth was decreased in ABCA1-silenced epithelial lung carcinoma cells. These data indicate an important role for ABCA1 in intracellular bacterial infection.
10.1016/j.micpath.2013.05.006
Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer.
Oncotarget
Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity. In mice with myeloid-specific loss of ABCA1 ( ; A1), tumor growth was inhibited by ∼4.8-fold relative to wild type (WT) animals. (G1) animals were also protected by 2.5-fold relative to WT, with no further inhibition of tumor growth in / myeloid-specific double knockout animals (DKO). Analyses of tumor-infiltrating immune cells revealed a correlation between tumor protection and decreased presence of the immune suppressive myeloid-derived suppressor cell (MDSC) subsets, Ly-6GLy-6C and Ly-6GLy-6C cells. The growth of the syngeneic MB49 murine bladder cancer cells was also inhibited in A1 mice. Collectively, our studies provide further evidence for an immune modulatory role for cholesterol homeostasis pathways in cancer.
10.18632/oncotarget.18666
Liver X receptor reduces proliferation of human oral cancer cells by promoting cholesterol efflux via up-regulation of ABCA1 expression.
Kaneko Tetsuharu,Kanno Chihiro,Ichikawa-Tomikawa Naoki,Kashiwagi Korehito,Yaginuma Nanae,Ohkoshi Chihiro,Tanaka Mizuko,Sugino Takashi,Imura Tetsuya,Hasegawa Hiroshi,Chiba Hideki
Oncotarget
Liver X receptors (LXRs) contribute not only to maintain cholesterol homeostasis but also to control cell growth. However, the molecular mechanisms behind the LXR-mediated anti-proliferative effects are largely unknown. Here we show, by immunohistochemistry, that LXRα and LXRβ are differentially distributed in oral stratified squamous epithelia. By immunohistochemical and Western blot analyses, we also reveal that LXRα is abundantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines. Cell counting, BrdU labeling and cell cycle assay indicated that LXR stimulation led to significant reduction of proliferation in HOSCC cells. Importantly, our study highlights, by using RNA interference, that the ATP-binding cassette transporter A1 (ABCA1)-accelerated cholesterol efflux is critical for the growth inhibitory action of LXRs in HOSCC cells. Moreover, we demonstrate that LXR activation reduces the growth of xenograft tumour of HOSCC cells in mice accompanied by the upregulation of ABCA1 expression and the decline of cholesterol levels in the tumour. These findings strongly suggested that targeting the LXR-regulated cholesterol transport, yielding in lowering intracellular cholesterol levels, could be a promising therapeutic option for certain types of cancers.
10.18632/oncotarget.5428
Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients.
Chou Jian-Liang,Huang Rui-Lan,Shay Jacqueline,Chen Lin-Yu,Lin Sheng-Jie,Yan Pearlly S,Chao Wei-Ting,Lai Yi-Hui,Lai Yen-Ling,Chao Tai-Kuang,Lee Cheng-I,Tai Chien-Kuo,Wu Shu-Fen,Nephew Kenneth P,Huang Tim H-M,Lai Hung-Cheng,Chan Michael W Y
Clinical epigenetics
BACKGROUND:The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family, ABCA1 was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that ABCA1 may be involved in ovarian cancer and its initiation. RESULTS:We first compared the expression level of ABCA1 in IOSE cells and a panel of ovarian cancer cell lines and found that ABCA1 was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of ABCA1 in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of ABCA1 increased the cholesterol level and promoted cell growth in vitro and in vivo. Further analysis of ABCA1 methylation in 76 ovarian cancer patient samples demonstrated that patients with higher ABCA1 methylation are associated with high stage (P = 0.0131) and grade (P = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of ABCA1 have shorter overall survival (P = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival (P = 0.038). CONCLUSIONS:ABCA1 may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients.
10.1186/s13148-014-0036-2
Tumor necrosis factor-alpha and lymphotoxin-alpha increase macrophage ABCA1 by gene expression and protein stabilization via different receptors.
Edgel Kimberly A,Leboeuf Renée C,Oram John F
Atherosclerosis
OBJECTIVE:The tumor necrosis factor superfamily may exert cardioprotective or atherogenic effects, depending on the state of lesion progression. Tumor necrosis factor-alpha (TNF) induces macrophage ATP-binding cassette transporter A1 (ABCA1), a cardioprotective transmembrane protein that exports cellular cholesterol to apolipoprotein A-I. Here we examined the role of TNF receptors (TNFRs) in ABCA1 induction and tested the effects of lymphotoxin-alpha (LT), another TNF family member, on macrophage ABCA1 levels. METHODS:Primary macrophages taken from mice deficient in TNF receptors were used to determine ABCA1 expression and cholesterol efflux activity in response to treatment with exogenous TNF or LT. RESULTS:We studied TNFR2(-/-) and TNFR1(-/-)/R2(-/-) mice and found that both receptors are necessary for maximal induction of ABCA1 by TNF. Peritoneal macrophages from TNFR1(-/-)/R2(-/-) mice had no change in ABCA1 mRNA levels when treated with TNF while cells from TNFR2(-/-) mice had ABCA1 mRNA levels that were half that of wild-type (WT) cells. In contrast, incubating TNFR1(-/-)/R2(-/-) mice with LT increased ABCA1 by stabilizing the protein, which was not observed in WT mice and this was associated with downstream signaling through the LTbeta receptor. CONCLUSION:TNF requires both of its receptors to maximally induce ABCA1. Despite previous studies suggesting that LT has proatherogenic properties, we found that LT increases ABCA1 protein in TNFR1(-/-)/R2(-/-) but not WT macrophages and may supplement TNF in enhancing ABCA1-dependent cholesterol export from early atherosclerotic lesions.
10.1016/j.atherosclerosis.2009.10.019
LXRβ controls glioblastoma cell growth, lipid balance, and immune modulation independently of ABCA1.
Patel Deven,Ahmad Fahim,Kambach Diane M,Sun Qian,Halim Alan S,Kramp Tamalee,Camphausen Kevin A,Stommel Jayne M
Scientific reports
Cholesterol is a critical component of membranes and a precursor for hormones and other signaling molecules. Previously, we showed that unlike astrocytes, glioblastoma cells do not downregulate cholesterol synthesis when plated at high density. In this report, we show that high cell density induces ABCA1 expression in glioblastoma cells, enabling them to get rid of excess cholesterol generated by an activated cholesterol biosynthesis pathway. Because oxysterols are agonists for Liver X Receptors (LXRs), we investigated whether increased cholesterol activates LXRs to maintain cholesterol homeostasis in highly-dense glioblastoma cells. We observed that dense cells had increased oxysterols, which activated LXRβ to upregulate ABCA1. Cells with CRISPR-mediated knockdown of LXRβ, but not ABCA1, had decreased cell cycle progression and cell survival, and decreased feedback repression of the mevalonate pathway in densely-plated glioma cells. LXRβ gene expression poorly correlates with ABCA1 in glioblastoma patients, and expression of each gene correlates with poor patient prognosis in different prognostic subtypes. Finally, gene expression and lipidomics analyses cells revealed that LXRβ regulates the expression of immune response gene sets and lipids known to be involved in immune modulation. Thus, therapeutic targeting of LXRβ in glioblastoma might be effective through diverse mechanisms.
10.1038/s41598-019-51865-8
Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.
Chen Jian-Hui,Zheng Yu-Long,Xu Chuan-Qin,Gu Li-Zhi,Ding Zong-Li,Qin Ling,Wang Yi,Fu Ran,Wan Yu-Feng,Hu Cheng-Ping
Biological chemistry
Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.
10.1515/hsz-2016-0307
MiR-183 functions as an oncogene by targeting ABCA1 in colon cancer.
Bi Da-Peng,Yin Cheng-Hua,Zhang Xiao-Yue,Yang Na-Na,Xu Jia-You
Oncology reports
Colon cancer remains the second most common cause of cancer-related death, indicating that a proportion of cancer cells are not eradicated by current therapies. Investigation of the molecular mechanisms involved in the development and progression of the disease will aid in the further understanding of the pathogenesis and progression and offer new targets for effective therapies. In the present study, we initially confirmed that ABCA1 was aberrantly expressed in colon cancer tissues and colon cancer cells. Its overexpression inhibited the proliferation of colon cancer HCT116 cells while silencing of ABCA1 promoted the proliferation and inhibited the apoptosis of colon cancer LDL1 cells. Upregulation of specific miRNAs can contribute to the downregulation of tumor-suppressive genes. Thus, we aimed to ascertain whether ABCA1 is downregulated by overexpression of a specific miRNA in colon cancer. We screened microRNAs that may target ABCA1 by miRanda which is a commonly used prediction algorithm. We found that miR-183 targets the 3'UTR of ABCA1 mRNA. Subsequent experiments confirmed that miR-183 degraded ABCA1 mRNA in the colon cancer cells. Finally, we demonstrated that miR-183 promoted the proliferation and inhibited the apoptosis of colon cancer cells. Thus, we conclude that miR-183 promotes proliferation and inhibits apoptosis by degrading ABCA1 in colon cancer.
10.3892/or.2016.4631
Role of ATP-binding cassette transporters in cancer initiation and progression.
Nobili Stefania,Lapucci Andrea,Landini Ida,Coronnello Marcella,Roviello Giandomenico,Mini Enrico
Seminars in cancer biology
ATP Binding Cassette (ABC) transporters, widely studied in cancer for their role in drug resistance, have been more recently also considered for their contribution to cancer cell biology. To date, many data provide evidences for their potential role in all the phases of cancer development from cancer susceptibility, tumor initiation, tumor progression and metastasis. Although many evidences are based on correlative analyses, data describing a direct or indirect role of ABC transporters in cancer biology are increasing. Overall, current available information suggests a relevant molecular effector role of some ABC transporters in cancer invasion and metastasis as reported in experimental tumor models. From a therapeutic point of view, due to the physiological relevant roles that ABC transporters play in the organism, the capability to selectively inhibit the function or the expression of ABC transporters in cancer stem cells or other tumor cells, represents the main challenge for researcher scientists. A detailed and updated description of the current knowledge on the role of ABC transporters in cancer biology is provided.
10.1016/j.semcancer.2019.08.006