Regulation of SLC1A4 and SLC1A5 in Prostate Cancer—Response

White, Mark A.; Frigo, Daniel E.

doi:10.1158/1541-7786.mcr-18-0240

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…A therapeutic strategy targeting GLS1 will bypass the complex upstream signaling pathways and directly suppress the production of energy and building blocks required by PCa cells, starving tumor cells to death. Since metabolic activity directly controls cellular proliferation (49,50), it may be more difficult for the tumor cells to overcome a metabolic inhibition to develop resistance. 3) ARtargeted treatment approaches will not work for PCa cells in which AR activity is not required such as in AR indifferent tumors (30) and SCNC (12).…”

Section: Discussionmentioning

confidence: 99%

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer

Yin

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Cellular metabolism in cancer is significantly altered to support the uncontrolled tumor growth. How metabolic alterations contribute to hormonal therapy resistance and disease progression in prostate cancer (PCa) remains poorly understood. Here we report a glutaminase isoform switch mechanism that mediates the initial therapeutic effect but eventual failure of hormonal therapy of PCa. Androgen deprivation therapy inhibits the expression of kidney-type glutaminase (KGA), a splicing isoform of glutaminase 1 (GLS1) up-regulated by androgen receptor (AR), to achieve therapeutic effect by suppressing glutaminolysis. Eventually the tumor cells switch to the expression of glutaminase C (GAC), an androgen-independent GLS1 isoform with more potent enzymatic activity, under the androgen-deprived condition. This switch leads to increased glutamine utilization, hyperproliferation, and aggressive behavior of tumor cells. Pharmacological inhibition or RNA interference of GAC shows better treatment effect for castration-resistant PCa than for hormone-sensitive PCa in vitro and in vivo. In summary, we have identified a metabolic function of AR action in PCa and discovered that the GLS1 isoform switch is one of the key mechanisms in therapeutic resistance and disease progression.

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Section: Discussionmentioning

confidence: 99%

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer

Yin

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…[6][7][8][9][10] Increasing studies have shown that SLC1A5 mediated the uptake of glutamine, which is an essential amino acid equipped with multiple functions such as nucleotide synthesis, protein synthesis and mTORC1 signaling pathway activation for rapid tumor cell proliferation. 27 In human breast cancer, a pharmacological inhibitor of SLC1A5 transport function prominently decreased the glutamine uptake, subsequently led to the inhibition of mTORC1 signaling, cell growth and cell cycle process. 28 And the lower expression of SLC1A5 endowed a better survival advantage in the xenografted mice.…”

Section: Discussionmentioning

confidence: 99%

Aberrant SLC6A14 Expression Promotes Proliferation and Metastasis of Colorectal Cancer via Enhancing the JAK2/STAT3 Pathway

Mao¹,

Sheng²,

Jia³

et al. 2021

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“…30 SLC1A4 (solute carrier family 1 member 4) encodes the alanine, serine, cysteine, and threonine exchanger 1 (ASCT1) 31 protein. It is a glutamine transporter 32 that is upregulated (≥2 fold) in erastin-treated samples. 33 In summary, eight genes (NOX4, ATG16L1, MYB, TGFBR1, LONP1, NF2, DUSP1, SLC1A4) in the prognostic model were overexpressed in ferroptosis, while the other two (NFE2L2, HIF1A) were not.…”

Section: Discussionmentioning

confidence: 99%

Novel ferroptosis-related gene signature as a potential prognostic tool for gastric cancer

et al. 2022

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Objectives Gastric cancer (GC) is a major global health concern and is difficult to diagnose in the early stage. Ferroptosis is an iron-dependent, novel form of non-apoptotic cell death. In recent years, inducing the upregulation of ferroptosis-related genes has become a promising therapeutic alternative for cancers, especially those resistant to traditional treatments. However, the relationship between ferroptosis-related genes and GC remains to be further elucidated. Methods In the present study, mRNA expression profiles and corresponding clinical data of patients with GC were retrieved from The Cancer Genome Atlas and used as test data. A multigene signature was constructed using the least absolute shrinkage and selection operator Cox regression model. Data of patients with GC from ‘GSE84426’ in the Gene Expression Omnibus database were used as Training data for validation. Results More than half ferroptosis-related genes were differentially expressed in GC tissues and adjacent normal tissue samples (58.43%) in the test data. Univariate Cox regression analysis showed that 16 differentially expressed genes were related to the prognosis of GC (all p < 0.05). Expression profiles of the 16 DGEs were analysed using LASSO Cox regression, and a prognostic model was established by selecting the 10 best genes for λ. These 10 genes were used to construct a 10-gene signature and stratify patients into two risk groups. Based on the median risk score in the test data, patients with GC were divided into high- and low-risk groups ( p < 0.001). Risk score was an independent predictor for overall survival in multivariate Cox regression analyses ( p < 0.001 and <0.01 in the test and training data, respectively; hazard ratio >1). Receiver operating characteristic curve analysis confirmed the predictive capacity of the 10-gene signature. Functional analysis revealed that tumour-infiltrating lymphocytes, antigen-presenting cell co-stimulation, and cytokine-cytokine receptors were enriched; however, the immune status differed between the two risk groups. Conclusion The novel ferroptosis-related gene signature can be used for GC prognosis. In addition, ferroptosis may provide a novel alternative for the diagnosis and treatment of GC.

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Regulation of SLC1A4 and SLC1A5 in Prostate Cancer—Response

Cited by 6 publications

References 11 publications

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer

Aberrant SLC6A14 Expression Promotes Proliferation and Metastasis of Colorectal Cancer via Enhancing the JAK2/STAT3 Pathway

Novel ferroptosis-related gene signature as a potential prognostic tool for gastric cancer

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