Prostate cancer: 4 big questions

Hodson, Richard

doi:10.1038/528s137a

Cited by 40 publications

(8 citation statements)

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“…Unfortunately, once PCa has spread to the lymph nodes and bones, the outlook is poor. The 5-year survival rate for metastatic cancer is one-third of that for localized disease [3]. Statistically, 25% of men with PCa worldwide develop metastatic disease and the 5-year survival of patients with metastasis to a distant site is significantly reduced to 29% [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

Jeon

Kwon

et al. 2019

PLoS ONE

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Prostate cancer (PCa) is the most common cancer among men worldwide. Most PCa cases are not fatal; however, the outlook is poor when PCa spreads to another organ. Bone is the target organ in about 80% of patients who experience metastasis from a primary PCa tumor. In the present study, we characterized the secretome of PC3/nKR cells, which are a new subline of PC3 cells that were originally isolated from nude mice that were implanted with PC3 cells without anti-natural killer (NK) cell treatment. Wound healing and Transwell assays revealed that PC3/nKR cells had increased migratory and invasive activities in addition to a higher resistance to NK cells-induced cytotoxicity as compared to PC3 cells. We quantitatively profiled the secreted proteins of PC3/nKR and PC3 cells by liquid chromatography-tandem mass spectrometry analysis coupled with 2-plex tandem mass tag labeling. In total, 598 secretory proteins were identified, and 561 proteins were quantified, among which 45 proteins were secreted more and 40 proteins were secreted less by PC3/nKR cells than by PC3 cells. For validation, the adapter molecule crk, serpin B3, and cystatin-M were analyzed by western blotting. PC3/nKR cells showed the selective secretion of NKG2D ligand 2, HLA-A, and IL-6, which may contribute to their NK cell-mediated cytotoxicity resistance, and had a high secretion of crk protein, which may contribute to their high migration and invasion properties. Based on our secretome analysis, we propose that PC3/nKR cells represent a new cell system for studying the metastasis and progression of PCa.

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Section: Introductionmentioning

confidence: 99%

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

Jeon

Kwon

et al. 2019

PLoS ONE

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“…PCa was initially considered a cancer of the elderly, but PCa incidence in patients below age 55 is currently increasing by more than 10% in the United States [2]. Although the 5-year survival rate of localized PCa is > 99%, the outlook is relatively poor once PCa advances [3,4]. Half of the men with castration-resistant PCa (CRPC) developed bone metastasis within two years of CRPC diagnosis [5].…”

Section: Introductionmentioning

confidence: 99%

SIRT5 is the desuccinylase of LDHA as novel cancer metastatic stimulator in aggressive prostate cancer

Kwon

Bang

Choi

et al. 2021

Preprint

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Prostate cancer (PCa) is the most commonly diagnosed genital cancer in men worldwide. Among patients who developed advanced PCa, 80% suffered from bone metastasis, with a sharp drop in the survival rate. Despite great efforts, the details of the mechanisms underlying castration-resistant PCa (CRPC) remains unclear. SIRT5, an NAD+-dependent desuccinylase, is hypothesized to be a key regulator of various cancers. However, compared to other SIRTs, the role of SIRT5 in cancer has not been extensively studied. Here, we showed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa stages. The correlation between the decrease in the SIRT5 level and the patients survival rate was also confirmed. Using quantitative global succinylome analysis, we characterized a significant increase of lysine 118 succinylation (K118su) of lactate dehydrogenase A (LDHA), which plays a role in increasing LDH activity. As a substrate of SIRT5, LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa patients. This study investigated the reduction of SIRT5 and LDHA-K118su as a novel mechanism involved in PCa progression. It can also be proposed as a new target that can prevent castration-resistant PCa progression, which is key to PCa treatment.

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“…Age, family history, and race are the most consistently observed risk factors associated with prostate cancer. Especially age and inherited factors are estimated to be responsible for 5% to 9% percentage of this disease2. Recently, molecular biological and epidemiological studies results suggest that the pathogenesis of prostate cancer may be associated with single nucleotide polymorphisms (SNPs) among several genes3–4.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 gene -572G/C polymorphism and prostate cancer risk

Wang¹,

Chen²,

Chen³

2018

Afr H. Sci.

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BackgroundThe aim of the present study was to determine whether the interleukin-6 (IL-6) -572G/C polymorphism correlates with prostate cancer.MethodsAccording to inclusion and exclusion criteria, the association of the IL-6 -572G/C polymorphism with prostate cancer was searched in databases and analyzed using comprehensive meta-analysis software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations.ResultsWe considered a total of six case-control studies including 2237 patients and 1754 controls and the meta-analysis results showed significant association between the IL-6 -572G/C polymorphism and prostate cancer risk(CC vs GG: OR = 0.49, 95% CI =0.37–0.65;CG vs GG: OR =0.71, 95% CI = 0.58–0.87; the dominant model: OR =0.65, 95% CI = 0.54–0.79;the recessive model: OR =0.70, 95% CI = 0.58–0.85). In stratified analyses by ethnicity, significant associations were found among Asian populations. However, no significant association was found in Caucasian populations.ConclusionOur findings demonstrated that the -572G/C polymorphism of the IL-6 gene may be a risk factor for the development of prostate cancer in Asians.

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Prostate cancer: 4 big questions

Cited by 40 publications

References 0 publications

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

SIRT5 is the desuccinylase of LDHA as novel cancer metastatic stimulator in aggressive prostate cancer

Interleukin-6 gene -572G/C polymorphism and prostate cancer risk

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