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A. Cell viability after CPT1Av2 silencing in MCF-7 ( A1 ), SK-BR-3 ( A2 ) and MDA-MB-231 ( A3 ) cells. Dye exclusion test (trypan blue staining) performed in cells transfected for 72h with siRNA2 at different concentrations. Decreased viability was significant at 70 nM CPT1A2 siRNAs. The cell viability on SK-BR-3 and MDA-MB-231 and the apoptotic assay were performed at 70nM siRNAs concentration. Results are mean values ± standard deviations of three independent experiments. * P = 0.05, siRNA2 versus NC. ** P <0.001, siRNA2 versus NC. B. Apoptosis detection with Annexin V (FITC) and propidium iodide (red) staining (40X magn.) The cells seeded in 4 wells/chamberslides were transfected for 72h with scrambled sequence (NC) or CPT1A siRNA2. Silenced cells showed early (Ann+, PI-) and late (Ann+, PI+) apoptotic events (arrows), as compared with un-treated cells. C. HOECHST DNA staining. Images show representative results of three independent experiments. Arrows indicates apoptotic figures and nuclear fragmentation. 5mM sodium butyrate was added in culture 48h after silencing (72h full incubation time), or alone for 24h. A particular of a nucleus is shown in the upper right side. Original magnification 100X. D. The results of HOECHST staining obtained from three independent experiments are given as percentage of apoptotic figures per total cell nuclei number. Asterisks indicates statistical significant differences ( P ≤0.05) in treated cells versus scrambled control (NC). Butyrate alone was able to induce apoptotic cell death also in MCF-12F control cells. E. CASPASE-9 expression in protein extracts from CPT1Av2 silenced (siRNA 2 ) or/and treated with 5mM sodium-butyrate (NaB) MCF-7 cells versus scrambled control (NC).
Source publication
Transcriptional mechanisms epigenetically-regulated in tumoral tissues point out new targets for anti-cancer therapies. Carnitine palmitoyl transferase I (CPT1) is the rate-limiting enzyme in the transport of long-chain fatty acids for β-oxidation. Here we identified the tumor specific nuclear CPT1A as a product of the transcript variant 2, that do...
Contexts in source publication
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... transfections were performed also in MDA- MB-231 and SK-BR-3 breast cancer cells in order to define the role of CPTIA variant2 in cell proliferation also in these different phenotypes. As previously observed in MCF7 a strong inhibition of proliferation and cell death induction was observed also in SK-BR-3 ( Figure 3A 2 ) and in the basal cell line MDA-MB-231 ( Figure 3A 3 ), confirming a potential role of this variant also in these breast cancer cells. ...
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... transfections were performed also in MDA- MB-231 and SK-BR-3 breast cancer cells in order to define the role of CPTIA variant2 in cell proliferation also in these different phenotypes. As previously observed in MCF7 a strong inhibition of proliferation and cell death induction was observed also in SK-BR-3 ( Figure 3A 2 ) and in the basal cell line MDA-MB-231 ( Figure 3A 3 ), confirming a potential role of this variant also in these breast cancer cells. ...
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... V and propidium iodide (PI) staining displayed early (annexin positive, PI negative) and late (annexin positive, PI positive) apoptotic events in siRNA2 transfected cells, as compared with mock- transfected control cells ( Figure 3B). DNA staining was performed with HOECHST fluorescent dye, 72h after silencing. ...
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... staining was performed with HOECHST fluorescent dye, 72h after silencing. As expected, butyrate alone caused nuclear fragmentation, both in MCF-7 cells ( Figure 3C) and in MCF12F control cells ( Figure 3C, right). In contrast, siRNA 2 silencing was mainly efficient in inducing apoptotic bodies in MCF-7 cells, whereas it was unable to trigger apoptosis in non neoplastic MCF12F cells. ...
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... staining was performed with HOECHST fluorescent dye, 72h after silencing. As expected, butyrate alone caused nuclear fragmentation, both in MCF-7 cells ( Figure 3C) and in MCF12F control cells ( Figure 3C, right). In contrast, siRNA 2 silencing was mainly efficient in inducing apoptotic bodies in MCF-7 cells, whereas it was unable to trigger apoptosis in non neoplastic MCF12F cells. ...
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... contrast, siRNA 2 silencing was mainly efficient in inducing apoptotic bodies in MCF-7 cells, whereas it was unable to trigger apoptosis in non neoplastic MCF12F cells. The treatment with HDAC-inhibitor butyrate in CPT1Av2 silenced MCF-7 cells did not improve the apoptotic effect ( Figure 3C and 3D). In addition in MCF7 cell line, defective for the functionality of Caspase 3, a strong induction of Caspase 9 was observed by western blot analysis in CPT1Av2 silenced cells. ...
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... addition in MCF7 cell line, defective for the functionality of Caspase 3, a strong induction of Caspase 9 was observed by western blot analysis in CPT1Av2 silenced cells. As shown in Figure 3E, the activation of caspase 9 was strongly induced in siRNA 2 treated cells. Similarly a strong induction of caspase 9 was observed in Na butyrate treated cells and in co-treated cells (siRNA 2 and Na-butyrate). ...
Citations
... Three different proteins belonging to the CPT1 family have been identified: CPT1A (or L-CPT1), CPT1B (or M-CPT1), and the most recently described variant, CPT1-C. While CPT1B is expressed only in brown adipose tissue, muscle, and heart, and CPT1C in the endoplasmic reticulum of neurons, CPT1A shows broader expression, and is found to be more localized in liver, pancreas, kidney, brain, blood, and embryonic tissues [31] . Compared with the muscle protein CPT1B, CPT1A shows higher affinity for its substrate (carnitine) and lower affinity for the physiological inhibitor malonyl-CoA [32] . ...
... Compared with the muscle protein CPT1B, CPT1A shows higher affinity for its substrate (carnitine) and lower affinity for the physiological inhibitor malonyl-CoA [32] . In recent years, CPT1A has generally been studied in correlation with several types of cancer, particularly breast and liver cancer, but according to recent evidence, this protein may be involved in the dysregulation of bone metabolism underlying the onset of osteoporosis [31] . Several studies have indeed identified many genetic loci associated with osteoporosis, but the functional mechanisms underlying these associations have rarely been investigated. ...
... In fact, mitochondria play a key role in several physiological processes not strictly related to energy metabolism alone, dysregulation of which can trigger a number of damaging events within the cell [44] . CPT1, a protein residing in the outer mitochondrial membrane and involved in the intracellular regulation of metabolism, transports longchain fatty acids into the mitochondria for β-oxidation, thus playing a primary role in the regulation of energy metabolism [31] . Studies in the literature have shown that this protein may potentially be involved in the onset of osteoporosis, its expression being correlated with BMD levels, but its possible role in the pathogenesis of sarcopenia has not been excluded. ...
The aging process results in progressive loss of muscle mass and strength, a condition known as sarcopenia. At biological-molecular level, this condition is characterized by numerous changes that occur in the muscle cell, such as increased protein degradation, apoptosis, altered autophagy process, impaired myogenic pathway, and mitochondrial dysfunction. The purpose of this concise review is to provide a brief overview of the involvement of mitochondria in the pathogenesis of sarcopenia, highlighting the potential involvement of carnitine palmitoyl transferase 1, an enzyme localized in the outer mitochondrial membrane, involved in the transport of long-chain fatty acids into the mitochondrion for β-oxidation. This protein is a potential new player in the pathogenesis of sarcopenia, since it may be responsible for the accumulation of fat mass and the development of insulin resistance in the muscle tissue of affected subjects, thus suggesting a new pathway underlying the onset and progression of the disease. KEY WORDS: Sarcopenia, mitochondria, muscle, mitochondrial dysfunction, energy metabolism.
... FISH and IF analysis visualised the co-localisation of endogenous circPSD3 and HDAC1 in the cytoplasm of HCC cells (Fig. 6G). Previous studies reported that HDAC1 binds to the promoter of SERPINB2 and regulates the expression of SER-PINB2 [44,45]. Our results also showed that HDAC1 knockdown significantly upregulated the expression of SERPINB2 in HCC cells (Fig. 6H), with corresponding changes in the protein levels of uPA and uPAR (Additional file 1: Fig. S8G). ...
... In MCF-7 breast cancer cells, HDAC1 interacts with CPT1A variant 2 (CPT1AV2). CPT1AV2 knockdown upregulates the levels of HDAC1 and alters the expression of multiple cancerrelated genes, including the downregulation of SER-PINB2 [45]. HDAC1 is significantly upregulated in HCC tissues compared to matched non-cancerous tissues. ...
Background
Vascular invasion is a major route for intrahepatic and distant metastasis in hepatocellular carcinoma (HCC) and is a strong negative prognostic factor. Circular RNAs (circRNAs) play important roles in tumorigenesis and metastasis. However, the regulatory functions and underlying mechanisms of circRNAs in the development of vascular invasion in HCC are largely unknown.
Methods
High throughput sequencing was used to screen dysregulated circRNAs in portal vein tumor thrombosis (PVTT) tissues. The biological functions of candidate circRNAs in the migration, vascular invasion, and metastasis of HCC cells were examined in vitro and in vivo. To explore the underlying mechanisms, RNA sequencing, MS2-tagged RNA affinity purification, mass spectrometry, and RNA immunoprecipitation assays were performed.
Results
circRNA sequencing followed by quantitative real-time PCR (qRT-PCR) revealed that circRNA pleckstrin and Sect. 7 domain containing 3 (circPSD3) was significantly downregulated in PVTT tissues. Decreased circPSD3 expression in HCC tissues was associated with unfavourable characteristics and predicted poor prognosis in HCC. TAR DNA-binding protein 43 (TDP43) inhibited the biogenesis of circPSD3 by interacting with the downstream intron of pre-PSD3. circPSD3 inhibited the intrahepatic vascular invasion and metastasis of HCC cells in vitro and in vivo. Serpin family B member 2 (SERPINB2), an endogenous bona fide inhibitor of the urokinase-type plasminogen activator (uPA) system, is the downstream target of circPSD3. Mechanistically, circPSD3 interacts with histone deacetylase 1 (HDAC1) to sequester it in the cytoplasm, attenuating the inhibitory effect of HDAC1 on the transcription of SERPINB2. In vitro and in vivo studies demonstrated that circPSD3 is a promising inhibitor of the uPA system.
Conclusions
circPSD3 is an essential regulator of vascular invasion and metastasis in HCC and may serve as a prognostic biomarker and therapeutic target.
... Many types of cancer appear to rely on FAO as an important source of ATP for rapid growth [29] . In breast cancer cells, downregulation of CPT1 regulates histone acetylation levels and induces histone deacetylase (HDAC) inhibition, promoting apoptosis, inhibiting angiogenesis, and downregulating genes associated with poor prognosis, invasion and metastasis [30] . Impaired proliferation and migration of lymphatic ECs in the absence of CPT1A in vivo can lead to lymphoid defects [31] , demonstrating its epigenetic regulatory function. ...
Multiple theories have been proposed to explain the pathogenesis of early-onset preeclampsia (EOPE), and angiogenic dysfunction is an important part of the pathogenesis. Carnitine palmitoyltransferase (CPT1A) is a key rate-limiting enzyme in the metabolic process of fatty acid oxidation (FAO). FAO regulates endothelial cell (EC) proliferation during vascular germination and is also essential for ab initio deoxyribonucleotide synthesis, but its role in EOPE needs to be further elucidated. In the present study, we investigated its functional role in EOPE by targeting the circHIPK3/miR-124-3p/CPT1A axis. In our study, reduced expression of circHIPK3 and CPT1A and increased expression of miR-124-3p in placental tissues from patients with EOPE were associated with EC dysfunction. Here, we confirmed that CPT1A regulates fatty acid oxidative activity, cell proliferation, and tube formation of ECs by regulating FAO. Functionally, knockdown of circHIPK3 suppressed EC angiogenesis by inhibiting CPT1A-mediated fatty acid oxidative activity, which was ameliorated by CPT1A overexpression. In addition, circHIPK3 regulates CPT1A expression by sponging miR-124-3p. Hence, circHIPK3 knockdown reduced the fatty acid oxidative process in ECs by sponging miR-124-3p in a CPT1A-dependent manner and inhibited EC proliferation and tube formation, which may have led to aberrant angiogenesis in EOPE. Thus, strategies targeting CPT1A-driven FAO may be a promising approach for the treatment of EOPE.
... From an application perspective, the development of new chemotherapeutic agents for the treatment of mammary tumours in dogs is therefore urgently needed. Several studies have identified carnitine palmitoyl transferase 1 A (CPT1A) as a druggable target for various cancers, and targeting CPT1A has been shown to have anti-cancer effects [27][28][29][30][31]. The aminocarnitine derivative teglicar (R)-N-(tetradecylcarbamoyl)-aminocarnitine (ST1326), a selective and reversible inhibitor of CPT1A originally used as a drug candidate for diabetes therapy [32,33], also plays a central role in the therapy of certain cancers. ...
... These findings are consistent with a previous study in which the authors demonstrated that teglicar induces apoptosis and inhibits the growth of human cervical cancer cells via a caspase-dependent signalling pathway [34]. In addition, our results are also consistent with a previous report [28], in which the authors demon-strated that inhibition of CPT1A led to programmed cell death through upregulation of pro-apoptotic genes, including Caspase-9. ...
Canine mammary tumours (CMTs) are the most common cancer in intact female dogs. In addition to surgery, additional targeted and non-targeted therapies may offer survival benefits to these patients. Therefore, exploring new treatments for CMT is a promising area in veterinary oncology. CMT cells have an altered lipid metabolism and use the oxidation of fatty acids for their energy needs. Here we investigated the tumoricidal effects of teglicar, a reversible inhibitor of carnitine palmitoyl transferase 1A (CPT1A), the rate-limiting enzyme for fatty acid import into mitochondria, on two CMT cells, P114 and CMT-U229. Viability and apoptosis were examined in CMT cells using the crystal violet assay, trypan blue assay, and flow cytometry analysis. The expression of mediators of apoptosis signalling (e.g., caspase-9, caspase-8, and caspase-3) was assessed by quantitative real-time polymerase chain reaction and western blot analyses. Teglicar was able to decrease cell viability and induce apoptosis in P114 and CMT-U229 cells. At the molecular level, the effect of teglicar was associated with an upregulation of the mRNA expression levels of caspase-9, caspase-8, and caspase-3 and an increase in their protein levels. In summary, our results show that teglicar has a potential effect against CMTs through the induction of apoptotic cell death, making it a promising therapeutic agent against CMTs.
... Fatty acid oxidation (FAO): FAO is the mitochondrial aerobic process of breaking down fatty acid (FA) into acetyl-CoA-units [123]. Overexpression of carnitine palmitoyl transferase I (CPTI), a rate-limiting enzyme of FAO, is associated with breast cancer progression [124][125][126]. FAO contributes to elevated ATP in TNBC and metastasis [127,128], and promotes apoptosis-resistance of TNBC by increasing mitochondrial membrane lipids [129]. ...
Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer mortality in women. Despite the recent development of new therapeutics including targeted therapies and immunotherapy, triple-negative breast cancer remains an aggressive form of breast cancer, and thus improved treatments are needed. In recent decades, it has become increasingly clear that breast cancers harbor metabolic plasticity that is controlled by mitochondria. A myriad of studies provide evidence that mitochondria are essential to breast cancer progression. Mitochondria in breast cancers are widely reprogrammed to enhance energy production and biosynthesis of macromolecules required for tumor growth. In this review, we will discuss the current understanding of mitochondrial roles in breast cancers and elucidate why mitochondria are a rational therapeutic target. We will then outline the status of the use of mitochondria-targeting drugs in breast cancers, and highlight ClpP agonists as emerging mitochondria-targeting drugs with a unique mechanism of action. We also illustrate possible drug combination strategies and challenges in the future breast cancer clinic.
... Relatedly, lipids are a critical component of cell membranes, so it is not surprising that fatty acid oxidation is an increasingly well-established factor promoting cancer metastasis [4]. Carnitine palmitoyl transferase 1A (CPT1A) resides in the outer mitochondrial membrane [5] and is the first rate-limiting enzyme in fatty acid oxidation, via its role in mediating fatty acid entry into the mitochondria [2]. Increased CPT1 expression and/or activity would therefore be expected to contribute to increased cancer proliferation and, in turn, mortality, but, to our knowledge, this hypothesis remains surprisingly unproven. ...
... Using the brown fat ROI tool, the region of interest was drawn and projected through a range of slices. Fixed-volume spheres were drawn to measure mean thymidine uptake in tumor tissue, where only SUV parameters (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and the "any" voxel criteria were selected. Lean body mass-corrected standardized uptake values (SUV) were calculated. ...
... CPT1A is found in the liver, pancreas, kidney, brain, blood, and embryonic tissues [5]. The results of Fig 6 are partially expected because adipocytes are the predominant cell population in the breast, where they can secrete significant amounts of fatty acids as metabolic substrates for tumors [21]. ...
CPT1A is a rate-limiting enzyme in fatty acid oxidation and is upregulated in high-risk breast cancer. Obesity and menopausal status' relationship with breast cancer prognosis is well established, but its connection with fatty acid metabolism is not. We utilized RNA sequencing data in the Xena Functional Genomics Explorer, to explore CPT1A's effect on breast cancer patients' survival probability. Using [18F]-fluorothymidine positron emission tomography-computed tomography images from The Cancer Imaging Archive, we segmented these analyses by obesity and menopausal status. In 1214 patients, higher CPT1A expression is associated with lower breast cancer survivability. We confirmed a previously observed protective relationship between obesity and breast cancer in pre-menopausal patients and supported this data using two-sided Pearson correlations. Taken together, these analyses using open-access databases bolster the potential role of CPT1A-dependent fatty acid metabolism as a pathogenic factor in breast cancer.
... Several roles of fatty acid oxidation have been described in metastasizing cancer cells 1,2 . CPT1a deletion inhibits mammosphere formation of luminal cells 54 and a splice variant of CPT1a promotes histone deacetylase activity through a protein-protein interaction 55 . Moreover, ATP levels sustained by CPT1a activity activate Src through autophosphorylation 56 . ...
Metabolic rewiring is often considered an adaptive pressure limiting metastasis formation; however, some nutrients available at distant organs may inherently promote metastatic growth. We find that the lung and liver are lipid-rich environments. Moreover, we observe that pre-metastatic niche formation increases palmitate availability only in the lung, whereas a high-fat diet increases it in both organs. In line with this, targeting palmitate processing inhibits breast cancer-derived lung metastasis formation. Mechanistically, breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a-dependent manner. Concomitantly, lysine acetyltransferase 2a expression is promoted by palmitate, linking the available acetyl-CoA to the acetylation of the nuclear factor-kappaB subunit p65. Deletion of lysine acetyltransferase 2a or carnitine palmitoyltransferase 1a reduces metastasis formation in lean and high-fat diet mice, and lung and liver metastases from patients with breast cancer show coexpression of both proteins. In conclusion, palmitate-rich environments foster metastases growth by increasing p65 acetylation, resulting in a pro-metastatic nuclear factor-kappaB signaling.
... The complete oxidation of the produced Ac-CoA, NADH and FADH2 is then accomplished by the TCA and oxidative phosphorylation [12,56]. In BC, a tumor specific variant of CPT1 (CPT1A) that lost its ability of fatty acyl transport to the mitochondria promotes survival, resistance to apoptosis and invasion by a mechanism dependent on the increasing activity of HDAC in BC cells [57]. The regulation of lipids can influence cell redox balance through biosynthesis and the remodeling of polyunsaturated FA (PUFA) in cell membranes. ...
Breast cancer (BC) is a heterogeneous disease that can be triggered by genetic alterations in mammary epithelial cells, leading to diverse disease outcomes in individual patients. The metabolic heterogeneity of BC enhances its ability to adapt to changes in the tumor microenvironment and metabolic stress, but unfavorably affects the patient’s therapy response, prognosis and clinical effect. Extrinsic factors from the tumor microenvironment and the intrinsic parameters of cancer cells influence their mitochondrial functions, which consequently alter their lipid metabolism and their ability to proliferate, migrate and survive in a harsh environment. The balanced interplay between mitochondria and fatty acid synthesis or fatty acid oxidation has been attributed to a combination of environmental factors and to the genetic makeup, oncogenic signaling and activities of different transcription factors. Hence, understanding the mechanisms underlying lipid metabolic heterogeneity and alterations in BC is gaining interest as a major target for drug resistance. Here we review the major recent reports on lipid metabolism heterogeneity and bring to light knowledge on the functional contribution of diverse lipid metabolic pathways to breast tumorigenesis and therapy resistance.
... These reactions generate NADH and FADH2 in each round, which upon entering the electron transport chain produce ATP, directly resulting in increased cell survival and cell proliferation, with direct relevance to the metabolism of cancer cells [22][23][24]. CPT1A has been reported to be upregulated in numerous cancers, including breast cancer [25][26][27]. Its function has been described to play a role in lymphangiogenesis [28], intestinal stemness [29,30], and colorectal metastasis [27]. ...
Obesity is a known risk factor for the development of gastroesophageal reflux disease (GERD), Barrett’s Esophagus (BE) and the progression to esophageal adenocarcinoma. The mechanisms by which obesity contributes to GERD, BE and its progression are currently not well understood. Recently, changes in lipid metabolism especially in the context of a high fat diet have been linked to GERD and BE leading us to explore whether fatty acid oxidation plays a role in the disease progression from GERD to esophageal adenocarcinoma. To that end, we analyzed the expression of the rate-limiting enzyme, carnitine palmytoyltransferase 1A (CPT1A), in human tissues and cell lines representing different stages in the sequence from normal squamous esophagus to cancer. We determined uptake of palmitic acid, the most abundant fatty acid in human serum, with fluorescent dye-labeled lipids as well as functional consequences of stimulation with palmitic acid relevant to Barrett’s tumorigenesis, e.g., proliferation, characteristics of stemness and IL8 mediated inflammatory signaling. We further employed different mouse models including a genetic model of Barrett’s esophagus based on IL1β overexpression in the presence and absence of a high fat diet and deoxycholic acid to physiologically mimic gastrointestinal reflux in the mice. Together, our data demonstrate that CPT1A is upregulated in Barrett’s tumorigenesis and that experimental palmitic acid is delivered to mitochondria and associated with increased cell proliferation and stem cell marker expression.
... A splice variant of CPT-1A which is 11 amino acids shorter at the c-terminus, has been found to be expressed exclusively in the nuclei of the MCF7 (ER-positive) cell line when compared to the MCF12F cell line (nontumorigenic epithelial mammary cells) 22 . Pucci et al. found that this variant, CPT-1Av2, forms a more stable complex with histone deacetylase-1 (HDAC1) and thus regulates genes involved in apoptosis, cell proliferation and invasion epigenetically 22,23 . HDAC1, in turn, has been implicated in mechanisms of immune evasion 24 . ...
... In breast cancer cells, a shorter variant of CPT-1A, variant 2, has been identified in the MCF7 cell line 23 . This variant is located in the nucleus and has been shown to interact with HDAC1 forming a more stable complex illustrating a potentially important epigenetic role 23 and identifies acetylation as the link between CPT-1A and epigenetic regulation. ...
... In breast cancer cells, a shorter variant of CPT-1A, variant 2, has been identified in the MCF7 cell line 23 . This variant is located in the nucleus and has been shown to interact with HDAC1 forming a more stable complex illustrating a potentially important epigenetic role 23 and identifies acetylation as the link between CPT-1A and epigenetic regulation. Our network analysis probed epigenetic links by identifying associations between CPT-1A and the genes involved in epigenetic regulation in patients. ...
Breast cancer is the commonest malignancy of women and with its incidence on the rise, the need to identify new targets for treatment is imperative. There is a growing interest in the role of lipid metabolism in cancer. Carnitine palmitoyl-transferase-1 (CPT-1); the rate limiting step in fatty acid oxidation, has been shown to be overexpressed in a range of tumours. There are three isoforms of CPT-1; A, B and C. It is CPT-1A that has been shown to be the predominant isoform which is overexpressed in breast cancer. We performed a bioinformatic analysis using readily available online platforms to establish the prognostic and predictive effects related to CPT-1A expression. These include the KM plotter, the Human Protein Atlas, the cBioPortal, the G2O, the MethSurvand the ROC plotter. A Network analysis was performed using the Oncomine platform and signalling pathways constituting the cancer hallmarks, including immune regulation as utilised by NanoString. The epigenetic pathways were obtained from the EpiFactor website. Spearman correlations (r) to determine the relationship between CPT-1A and the immune response were obtained using the TISIDB portal. Overexpression of CPT-1A largely confers a worse prognosis and CPT-1A progressively recruits a range of pathways as breast cancer progresses. CPT-1A’s interactions with cancer pathways is far wider than previously realised and includes associations with epigenetic regulation and immune evasion pathways, as well as wild-type moderate to high penetrant genes involved in hereditary breast cancer. Although CPT-1A genomic alterations are detected in 9% of breast carcinomas, both the alteration and the metagene associated with it, confers a poor prognosis. CPT-1A expression can be utilised as a biomarker of disease progression and as a potential therapeutic target.
