Solute transporters and malignancy: establishing the role of uptake transporters in breast cancer and breast cancer metastasis

Sutherland, Rachel; Meeson, Annette; Lowes, Simon

doi:10.1007/s10555-020-09879-6

Cited by 39 publications

(32 citation statements)

References 105 publications

(197 reference statements)

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“…HCV up-regulated both mRNA and protein expression levels of SLC3A2 and exploits for its cellular entry [ 50 ]. SLC transporters have been reported in many cancers and further research is in progress to exploit their potentials as prognostic indicators and therapeutic targets [ 51 ]. In pancreatic cancer patients, overexpression of ABCC2 along with SLC22A3 in a combination was detected [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line

et al. 2021

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Hepatitis B virus (HBV) infection remains a major health issue worldwide and the leading cause of cirrhosis and hepatocellular carcinoma (HCC). It has been reported previously that HBV invasion can extensively alter transcriptome, the proteome of exosomes and host cell lipid rafts. The impact of HBV on host proteins through regulating their global post-translational modifications (PTMs), however, is not well studied. Viruses have been reported to exploit cellular processes by enhancing or inhibiting the ubiquitination of specific substrates. Nevertheless, host cell physiology in terms of global proteome and ubiquitylome has not been addressed yet. Here by using HBV-integrated HepG2.2.15 model cell line we first report that HBV significantly modify the host global ubiquitylome. As currently the most widely used HBV cell culture model, HepG2.2.15 can be cultivated for multiple generations for protein labeling, and can replicate HBV, express HBV proteins and secrete complete HBV Dane particles, which makes it a suitable cell line for ubiquitylome analysis to study HBV replication, hepatocyte immune response and HBV-related HCC progression. Our previous experimental results showed that the total ubiquitination level of HepG2.2.15 cell line was significantly higher than that of the corresponding parental HepG2 cell line. By performing a Ubiscan quantification analysis based on stable isotope labeling of amino acids in cell culture (SILAC) of HepG2.2.15 and HepG2 cell lines, we identified a total of 7188 proteins and the protein levels of nearly 19% of them were changed over 2-folds. We further identified 3798 ubiquitinated Lys sites in 1476 host proteins with altered ubiquitination in response to HBV. Our results also showed that the global proteome and ubiquitylome were negatively correlated, indicating that ubiquitination might be involved in the degradation of host proteins upon HBV integration. We first demonstrated the ubiquitination change of VAMP3, VAMP8, DNAJB6, RAB8A, LYN, VDAC2, OTULIN, SLC1A4, SLC1A5, HGS and TOLLIP. In addition, we described 5 novel host factors SLC1A4, SLC1A5, EIF4A1, TOLLIP and BRCC36 that efficiently reduced the amounts of secreted HBsAg and HBeAg. Overall, the HBV-mediated host proteome and ubiquitylome change we reported will provide a valuable resource for further investigation of HBV pathogenesis and host-virus interaction networks.

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Section: Discussionmentioning

confidence: 99%

Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line

et al. 2021

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“…The SLC family is relevant to the genesis and progression of various cancers [36][37][38]. SLC transporters for essential nutrients may promote tumor occurrence; however, some subtypes inhibit tumors by increasing the accumulation of anti-tumor drugs in cells [39]. Also, SLC transporters can mediate immune cell homeostasis through transporters of immune cells [40,41].…”

Section: Discussionmentioning

confidence: 99%

Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

et al. 2021

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The solute carrier family has been reported to play critical roles in the progression of several cancers; however, the relationship between solute carrier family 12 member 8 (SLC12A8) and bladder cancer (BC) has not been clearly confirmed. This study explores the prognostic value of SLC12A8 for BC and its correlation with immune cell infiltration. We found that the expression of SLC12A8 mRNA was significantly overexpressed in BC tissues compared with noncancerous tissues in multiple public databases, and the result was validated using real-time PCR and immunohistochemistry (IHC). The Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of SLC12A8 for BC. The high expression of SLC12A8 led to a shorter overall survival time and was an unfavorable prognostic biomarker for BC. The mechanisms of SLC12A8 promoting tumorigenesis were investigated by Gene Set Enrichment Analysis (GSEA). Moreover, the correlations of SLC12A8 expression with the tumor-infiltrating immune cells (TICs) in BC were explored using TIMER 2.0 and CIBERSORT. SLC12A8 was associated with CD4+ T cells, dendritic cells, neutrophils, and macrophages infiltration. The expression of SLC12A8 was positively correlated with crucial immune checkpoint molecules. In conclusion, SLC12A8 might be an unfavorable prognostic biomarker in BC related to tumor immune cell infiltration.

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“…Although SLC proteins have been relatively understudied over the past few years, they are now known to play vital roles in essential biological processes and human diseases ( César-Razquin et al, 2015 ; Rives et al, 2017 ; Schaller and Lauschke, 2019 ). In cancer, dysregulation of SLC proteins has been shown to be oncogenic ( Xie et al, 2011 ; Mohelnikova-Duchonova et al, 2013 ; Bhutia et al, 2016 ; Sutherland et al, 2020 ). Many SLCs have been reported to be aberrantly expressed in LUAD and might serve as prognostic biomarkers ( Ikeda et al, 2015 ; Lehrer and Rheinstein, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Zhu

Mou

et al. 2021

Front. Cell Dev. Biol.

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Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

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Solute transporters and malignancy: establishing the role of uptake transporters in breast cancer and breast cancer metastasis

Cited by 39 publications

References 105 publications

Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line

Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line

Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

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