Abnormal expression of ABCD3 is an independent prognostic factor for colorectal cancer

Zhang, Yujiao; Zhang, Yaqi; Wang, Jiping; Yang, Jiyuan; Yang, Guodong

doi:10.3892/ol.2020.11463

Cited by 9 publications

(12 citation statements)

References 35 publications

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“…Both ABCD1 and ABCD3 have low tissue specificity, and they are downregulated in renal cancer [75,75]. ABCD3 is also downregulated in colorectal cancer [75]. Downregulation leads to lipid accumulation in tissue which promotes carcinogenesis, indicating a protective role for peroxisomal transporters [72].…”

Section: Discussionmentioning

confidence: 99%

“…ABCD transporters regulate cellular response to oxidative stress and control inflammatory response by regulating peroxisomal b-oxidation of fatty acids [74]. Both ABCD1 and ABCD3 have low tissue specificity, and they are downregulated in renal cancer [75,75]. ABCD3 is also downregulated in colorectal cancer [75].…”

Section: Abcd3 Is the Most Abundant Liver Abc Transportermentioning

confidence: 99%

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Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin

et al. 2020

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ABC transporters traffic drugs and their metabolites across membranes, making ABC-transporter expression levels a key factor regulating local drug concentrations in different tissues and individuals. Yet, quantification of ABC transporters remains challenging because they are large and low-abundance transmembrane proteins. Here we analyzed 200 samples of crude and membrane-enriched fractions from human liver, kidney, intestine, brain microvessels, and skin, by label-free quantitative mass spectrometry. We identified 32 (out of 48) ABC transporters: ABCD3 was the most abundant in liver, whereas ABCA8, ABCB2/TAP1, and ABCE1 were detected in all tissues. Interestingly, this atlas unveiled that ABCB2/TAP1 may have TAP2-independent functions in the brain, and that biliary atresia and control livers have quite different ABCtransporter profiles. We propose that meaningful biological information can be derived from a direct comparison of these datasets.

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Section: Discussionmentioning

confidence: 99%

Section: Abcd3 Is the Most Abundant Liver Abc Transportermentioning

confidence: 99%

Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin

et al. 2020

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“…Biology 2020, 9, x FOR PEER REVIEW 4 of 38 the prognosis of colon cancer patients receiving 5-FU treatment with studies reporting both negative and positive correlations [20][21][22][23]. Nonetheless, incidence of 5-FU resistance is still consistently motivated by elevated levels of ABC transporters, that includes ABCB1 [P-glycoprotein (P-gp) or MDR1] [24,25]; ABCG2 [breast cancer resistance protein (BCRP)] [26,27]; ABCC1 [multidrug resistance-associated protein (MRP1)] [28,29]; ABCC3 [20], and ABCC2 [30].…”

Section: Alterations In Drug Transportsmentioning

confidence: 99%

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Azwar

Seow

Abdullah

et al. 2021

Biology

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5-Fluorouracil (5-FU) plus leucovorin (LV) remain as the mainstay standard adjuvant chemotherapy treatment for early stage colon cancer, and the preferred first-line option for metastatic colon cancer patients in combination with oxaliplatin in FOLFOX, or irinotecan in FOLFIRI regimens. Despite treatment success to a certain extent, the incidence of chemotherapy failure attributed to chemotherapy resistance is still reported in many patients. This resistance, which can be defined by tumor tolerance against chemotherapy, either intrinsic or acquired, is primarily driven by the dysregulation of various components in distinct pathways. In recent years, it has been established that the incidence of 5-FU resistance, akin to multidrug resistance, can be attributed to the alterations in drug transport, evasion of apoptosis, changes in the cell cycle and DNA-damage repair machinery, regulation of autophagy, epithelial-to-mesenchymal transition, cancer stem cell involvement, tumor microenvironment interactions, miRNA dysregulations, epigenetic alterations, as well as redox imbalances. Certain resistance mechanisms that are 5-FU-specific have also been ascertained to include the upregulation of thymidylate synthase, dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase, and the downregulation of thymidine phosphorylase. Indeed, the successful modulation of these mechanisms have been the game plan of numerous studies that had employed small molecule inhibitors, plant-based small molecules, and non-coding RNA regulators to effectively reverse 5-FU resistance in colon cancer cells. It is hoped that these studies would provide fundamental knowledge to further our understanding prior developing novel drugs in the near future that would synergistically work with 5-FU to potentiate its antitumor effects and improve the patient’s overall survival.

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“…This suggests a role of these ABC transporters in cell cycle control, cell differentiation, and tumorigenesis. Downregulation of peroxisomal ABC transporters has been observed in several cases: ABCD1 in melanoma [ 98 ] and renal cell carcinoma [ 99 ], ABCD2 in breast cancer [ 100 ], and ABCD3 in ovarian cancer [ 101 ] and colorectal cancer [ 102 ]. Moreover, a lower prognostic value has been associated with low expression of ABCD1 in ovarian cancer [ 103 ] and low expression of ABCD3 in colorectal cancer [ 102 ].…”

Section: Human Diseasesmentioning

confidence: 99%

“…Downregulation of peroxisomal ABC transporters has been observed in several cases: ABCD1 in melanoma [ 98 ] and renal cell carcinoma [ 99 ], ABCD2 in breast cancer [ 100 ], and ABCD3 in ovarian cancer [ 101 ] and colorectal cancer [ 102 ]. Moreover, a lower prognostic value has been associated with low expression of ABCD1 in ovarian cancer [ 103 ] and low expression of ABCD3 in colorectal cancer [ 102 ]. On the contrary, ABCD1 and ABCD3 were found upregulated in breast carcinoma [ 104 ], and a positive correlation was observed between ABCD3 expression and glioma tumor grades [ 105 ].…”

Section: Human Diseasesmentioning

confidence: 99%

Peroxisomal ABC Transporters: An Update

Tawbeh

Gondcaille

Trompier

et al. 2021

IJMS

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ATP-binding cassette (ABC) transporters constitute one of the largest superfamilies of conserved proteins from bacteria to mammals. In humans, three members of this family are expressed in the peroxisomal membrane and belong to the subfamily D: ABCD1 (ALDP), ABCD2 (ALDRP), and ABCD3 (PMP70). These half-transporters must dimerize to form a functional transporter, but they are thought to exist primarily as tetramers. They possess overlapping but specific substrate specificity, allowing the transport of various lipids into the peroxisomal matrix. The defects of ABCD1 and ABCD3 are responsible for two genetic disorders called X-linked adrenoleukodystrophy and congenital bile acid synthesis defect 5, respectively. In addition to their role in peroxisome metabolism, it has recently been proposed that peroxisomal ABC transporters participate in cell signaling and cell control, particularly in cancer. This review presents an overview of the knowledge on the structure, function, and mechanisms involving these proteins and their link to pathologies. We summarize the different in vitro and in vivo models existing across the species to study peroxisomal ABC transporters and the consequences of their defects. Finally, an overview of the known and possible interactome involving these proteins, which reveal putative and unexpected new functions, is shown and discussed.

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Abnormal expression of ABCD3 is an independent prognostic factor for colorectal cancer

Cited by 9 publications

References 35 publications

Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin

Mass spectrometry‐based abundance atlas of ABC transporters in human liver, gut, kidney, brain and skin

Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment

Peroxisomal ABC Transporters: An Update

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