Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans

Tang, Li; Zhu, Qianqian; Wang, Zinian; Shanahan, Clayton M.; Bensen, Jeannette T.; Fontham, Elizabeth T.H.; Smith, Gary J.; Pop, Elena; Azabdaftari, Gissou; Mohler, James L.; Wu, Yue

doi:10.1158/1055-9965.epi-20-1389

Cited by 4 publications

(1 citation statement)

References 51 publications

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“…A number of other pathologies have also been associated with SLCO2A1. Thus, recent studies have provided new evidence for the roles of the SLCO2A1 protein in carcinogenesis [160,[162][163][164][165][166], in experimental colitis [167], in the parturition process [168], in cigarette-smoke-induced lung inflammation [169], in a gastroesophageal reflux disease [170], and in the non-healing diabetic foot ulcer [171]. The role of the ion channel function of SLCO2A1 in the mechanism of development of these pathologies remains to be elucidated.…”

Section: Physiological/pathophysiological Implications Of Maxi-clmentioning

confidence: 99%

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

Sabirov

Islam

Okada

et al. 2021

Life

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The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large-conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans to frogs. A unitary conductance of 300–400 pS, linear current-to-voltage relationship, relatively high anion-to-cation selectivity, bell-shaped voltage dependency, and sensitivity to extracellular gadolinium are biophysical and pharmacological hallmarks of the Maxi-Cl channel. Its identification as a complex with SLCO2A1 as a core pore-forming component and two auxiliary regulatory proteins, annexin A2 and S100A10 (p11), explains the activation mechanism as Tyr23 dephosphorylation at ANXA2 in parallel with calcium binding at S100A10. In the resting state, SLCO2A1 functions as a prostaglandin transporter whereas upon activation it turns to an anion channel. As an efficient pathway for chloride, Maxi-Cl is implicated in a number of physiologically and pathophysiologically important processes, such as cell volume regulation, fluid secretion, apoptosis, and charge transfer. Maxi-Cl is permeable for ATP and other small signaling molecules serving as an electrogenic pathway in cell-to-cell signal transduction. Mutations at the SLCO2A1 gene cause inherited bone and gut pathologies and malignancies, signifying the Maxi-Cl channel as a perspective pharmacological target.

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Section: Physiological/pathophysiological Implications Of Maxi-clmentioning

confidence: 99%

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

Sabirov

Islam

Okada

et al. 2021

Life

View full text Add to dashboard Cite

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SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis

Rajanala,

Plym,

Vaselkiv

et al. 2023

Carcinogenesis

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Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3,208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians’ Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5,598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69 to 0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.

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Androgens and severity of the new coronavirus infection course

Грицкевич

Prokhorova

Baitman³

et al. 2022

Issled. prakt. med. (Print)

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The analysis results of work in the conditions of a pandemic of a new coronavirus infection pandemic showed that patients with malignant neoplasms (ZNO) belong to a group of high risk of infection and severe course of this infectious disease. The incidence of COVID‑19 complications in this group of patients is 3.5 times higher than in the general population, which is largely due to the immunosuppressive effect of both oncological diseases themselves and their treatment.Many attempts have been held to identify and validate other risk factors for severe COVID‑19. Epidemiological data indicate that elderly patients with chronic diseases, including diabetes mellitus (DM), arterial hypertension (AH), obesity, are susceptible to a more severe course of COVID‑19 with a higher frequency of deaths. A number of studies have noted a higher incidence of severe forms of the infectious process and a higher level of COVID‑19‑associated mortality in men. Currently new aspects of the influence of hormonal changes, including iatrogenic ones, on the course of coronavirus infection are being identified. In particular, the data of clinical studies demonstrate a correlation between the level of testosterone in the blood serum and the level of inflammatory cytokines, the features of viral entry into cells, the course of the disease as a whole. This is especially important for understanding the features of the new coronavirus infection in patients with prostate cancer (PC), including for the development of a therapeutic algorithm, indications and contraindications to certain methods of treating PC in a pandemic, as well as ways of additional therapeutic effects when combined with PC and COVID‑19.The review presents the results of studies on the potential mechanisms of increased susceptibility of men to SARS‑CoV‑2 and discusses the search for new therapeutic targets in COVID‑19, discusses the features of the course of COVID‑19 in patients with PC depending on the level of androgens, including androgen deprivation therapy (ADT).

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Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans

Cited by 4 publications

References 51 publications

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis

Androgens and severity of the new coronavirus infection course

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