Transcriptome analysis reveals an altered expression profile of zinc transporters in colorectal cancer

Barresi, Vincenza; Valenti, Giovanna; Spampinato, Giorgia; Musso, Nicolò; Castorina, Sergio; Rizzarelli, Enrico; Condorelli, D. F.

doi:10.1002/jcb.27285

Cited by 50 publications

(37 citation statements)

References 45 publications

(133 reference statements)

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“…ZIP6 has been implicated in oesophageal cancer [70,71], breast cancers [23] prostate cancer [72], consistently being associated with more aggressive forms of the diseases. Similarly, ZIP10 over-expression has been correlated to aggressiveness in renal cell carcinoma [36], metastatic breast cancer [35], gastric cancer [73] and it is one of the 7 zinc transporter genes upregulated in activated colon tumour cells [24], compatible with our proposed role for ZIP10 in cell division.…”

Section: Discussionsupporting

confidence: 61%

“…Accordingly, chelating zinc has been explored as a means to stop proliferative growth of cancer tissues [22]. The additional zinc seen in cancers is usually supplied by various zinc transporters from the SLC39A family [23] [24][25][26]. Two close homologues within this family, ZIP6 (SLC39A6, also known as LIV-1) and ZIP10 (SLC39A10) [27,28], with a 43.5% sequence identity, are on the same clade of the ZIP family phylogenetic tree [29] and have both been independently implicated in cancer [23,29].…”

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

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The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

Nimmanon

Ziliotto

Ogle

et al. 2020

Cell. Mol. Life Sci.

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Zinc has been known to be essential for cell division for over 40 years but the molecular pathways involved remain elusive. Cellular zinc import across biological membranes necessitates the help of zinc transporters such as the SLC39A family of ZIP transporters. We have discovered a molecular process that explains why zinc is required for cell division, involving two highly regulated zinc transporters, as a heteromer of ZIP6 and ZIP10, providing the means of cellular zinc entry at a specific time of the cell cycle that initiates a pathway resulting in the onset of mitosis. Crucially, when the zinc influx across this heteromer is blocked by ZIP6 or ZIP10 specific antibodies, there is no evidence of mitosis, confirming the requirement for zinc influx as a trigger of mitosis. The zinc that influxes into cells to trigger mitosis additionally changes the phosphorylation state of STAT3 converting it from a transcription factor to a protein that complexes with this heteromer and pS 38 Stathmin, the form allowing microtubule rearrangement as required in mitosis. This discovery now explains the specific cellular role of ZIP6 and ZIP10 and how they have special importance in the mitosis process compared to other ZIP transporter family members. This finding offers new therapeutic opportunities for inhibition of cell division in the many proliferative diseases that exist, such as cancer.

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Section: Discussionsupporting

confidence: 61%

Section: Cellular and Molecular Life Sciencesmentioning

confidence: 99%

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

Nimmanon

Ziliotto

Ogle

et al. 2020

Cell. Mol. Life Sci.

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“…High expression levels of SLC39A10 have been reported to be correlated with invasive behaviour by stimulating cell migration in breast cancer cells [44]. Similar observations have been made in the case of colorectal cancer [45] and renal cell carcinoma [46]. Cao et al (2019) [16] demonstrated that SLC39A10 was down-regulated in GBM tissues and positively associated with survival which is consistent with our finding in this study, but its role in GBM progression is poorly understood and requires further exploration in future studies.…”

Section: Discussionsupporting

confidence: 58%

Large-Scale Analysis Reveals Gene Signature for Survival Prediction in Primary Glioblastoma

Prasad

Tian

2020

Mol Neurobiol

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Glioblastoma multiforme (GBM) is the most aggressive and common primary central nervous system tumour. Despite extensive therapy, GBM patients usually have poor prognosis with a median survival of 12–15 months. Novel molecular biomarkers that can improve survival prediction and help with treatment strategies are still urgently required. Here we aimed to robustly identify a gene signature panel for improved survival prediction in primary GBM patients. We identified 2166 differentially expressed genes (DEGs) using meta-analysis of microarray datasets comprising of 955 samples (biggest primary GBM cohort for such studies as per our knowledge) and 3368 DEGs from RNA-seq dataset with 165 samples. Based on the 1443 common DEGs, using univariate Cox and least absolute shrinkage and selection operator (LASSO) with multivariate Cox regression, we identified a survival associated 4-gene signature panel including IGFBP2, PTPRN, STEAP2 and SLC39A10 and thereafter established a risk score model that performed well in survival prediction. High-risk group patients had significantly poorer survival as compared with those in the low-risk group (AUC = 0.766 for 1-year prediction). Multivariate analysis demonstrated that predictive value of the 4-gene signature panel was independent of other clinical and pathological features and hence is a potential prognostic biomarker. More importantly, we validated this signature in three independent GBM cohorts to test its generality. In conclusion, our integrated analysis using meta-analysis approach maximizes the use of the available gene expression data and robustly identified a 4-gene panel for predicting survival in primary GBM.

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“…SLC30A4 is significantly overexpressed in prostate cancer compared to normal tissues from other organs 22 . SLC30A5-7 and 9 are significantly upregulated in colorectal cancer and SLC30A9 is involved in the canonical Wnt pathway 24 . Overexpressed SLC30A7 in esophageal squamous cell carcinoma could be a mechanism adapted by tumor cells to maintain the basal zinc requirement for carrying out vital functions during zinc deficiency 54 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that SLC30A1 , 9 and 10 were significantly upregulated in prostate cancer tissues compared to normal tissues, while SLC30A5 - 6 were strongly downregulated 21 – 23 . Upregulated SLC30A5-7 expression might play a critical role in coordinating transcriptional programming associated with the increased activity of the early secretory pathway in colorectal cancer 24 . Nevertheless, the functional and prognostic significance of SLC30A family genes in GC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

Guo

2020

Sci Rep

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The solute carrier 30 (SLC30) family genes play a fundamental role in various cancers. However, the diverse expression patterns, prognostic value, and potential mechanism of SLC30A family genes in gastric cancer (GC) remain unknown. Herein, we analyzed the expression and survival data of SLC30A family genes in GC patients using multiple bioinformatic approaches. Expression data of SLC30A family genes for GC patients were extracted from the Cancer Genome Atlas (TCGA) and genetic alteration frequency assessed by using cBioportal database. And validated the expression of SLC30A family genes in GC tissues and corresponding normal tissues. The prognostic value of SLC30A family genes in gastric cancer patients were explored using Kaplan–Meier plotter database. Functional enrichment analysis performed using DAVID database and clusterProfiler package. And ssGSEA algorithm was performed to explore the relationship between the SLC30A family genes and the infiltration of immune cells. We found that the median expression levels of SLC30A1-3, 5–7, and 9 were significantly upregulated in gastric cancer tissues compared to non-cancerous tissues, while SLC30A4 was downregulated. Meanwhile, SLC30A1-7, and 9 were significantly correlated with advanced tumor stage and nodal metastasis status, SLC30A5-7, and 9–10 were significantly related to the Helicobacter pylori infection status of GC patients. High expression of five genes (SLC30A1, 5–7, and 9) was significantly correlated with better overall survival (OS), first progression survival (FPS), and post progression survival (PPS). Conversely, upregulated SLC30A2-4, 8, and 10 expression was markedly associated with poor OS, FP and PPS. And SLC30A family genes were closely associated with the infiltration of immune cells. The present study implied that SLC30A5 and 7 may be potential biomarkers for predicting prognosis in GC patients, SLC30A2 and 3 play an oncogenic role in GC patients and could provide a new strategy for GC patients treatment.

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Transcriptome analysis reveals an altered expression profile of zinc transporters in colorectal cancer

Cited by 50 publications

References 45 publications

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis

Large-Scale Analysis Reveals Gene Signature for Survival Prediction in Primary Glioblastoma

Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer

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