IL13Rα1 prevents a castration resistant phenotype of prostate cancer by targeting hexokinase 2 for ubiquitin-mediated degradation

Objective:Androgen deprivation therapy(ADT)is still the principal treatment option for prostate cancer(PCa).In addition to reactivation of androgen receptor signaling,the resistance of PCa to apoptosis during ADT also contributes to castration resistant PCa(CRPC).A previous study reported that gene transfer of IL-13Rα2 into PCa cells sensitized the cells to the IL-13R-targeted cytotoxin IL13Rα1,leading to apoptosis.Compared with IL-13Rα2,IL13Rα1 is more constitutively expressed in PCa cells,but its function in PCa remains to be established.Methods:We determined the role and expression of IL13Rα1 in PCa cancer cells using western blotting,flow cytometry,and cell proliferation assays.Co-immunoprecipitation and mass spectrometry were used to identify the proteins that interacted with IL13Rα1,to elucidate its function.Results:In this study,we showed that IL13Rα1 was selectively suppressed in androgen-deprived PCa cells and that its suppression tended to be associated with poor prognoses of PCa patients.IL13Rα1 overexpression promoted apoptosis and inhibited tumor growth under androgen-deprived or castrated conditions(P<0.01).Mechanistically,IL13Rα1 recruited and facilitated ubiquitin protein ligase E3C-mediated ubiquitination and degradation of hexokinase 2(HK2),resulting in glycolytic inhibition and eventually leading to PCa cell apoptosis.Furthermore,our data revealed that mutated ataxia-telangiectasia kinase phosphorylated and facilitated the selective ubiquitin proteasome-mediated degradation of HK2.Notably,IL13Rα1-overexpressing PCa cells were more susceptible to apoptosis and exhibited reduced tumor growth after exposure to the HK2 inhibitor,2-deoxy-D-glucose(P<0.01).Conclusions:Our data identified a tumor suppressor role for IL13Rα1 in preventing the resistance of PCa cells to apoptosis during androgen deprivation by inhibiting glycolysis.IL13Rα1-mediated signaling involving HK2 may therefore provide a novel treatment target and strategy for CRPC.

Improving anti-Gram-positive-bacterial performance and osteogenesis for zinc alloy via mussel mimetic polydopamine with non-antibiotic lysozyme and parathyroid hormone

In this work,a novel coating with a non-antibiotic agent for inhibiting Gram-positive bacteria and promoting osteogenesis was prepared on zinc-aluminium alloy(ZA6-1)via mussel mimetic polydopamine(PDA)containing lysozyme(LYS)and parathyroid hormone(PTH).The results indicate that as-deposited coatings can efficiently decrease the degradation rate of ZA6-1 from 0.52 to 0.16 mm/year,and the addition of LYS weakens the coating resistance,while the addition of PTH enhances the coating resis-tance.In spite that no obvious inhibition of Escherichia coli is observed,the coated zinc alloys show good in vitro antibacterial performance against Staphylococcus aureus.Compared with ZA6-1 zinc alloys,the increase of antibacterial efficacy reaches 86.9%-90.1%.Furthermore,the lower hydrophilicity(26.4°),higher osteoblast cell viability(>100%),good osteoblast cell morphology and better osteoblast cell differentiation(ALP=107.7%)for PDA-LYS/PTH coated samples support that as-prepared coating is promising for modifying biodegradable zinc implants.

高沥水性钝顶螺旋藻新品系的选育及超微结构与RAPD分析

[目的]选育高沥水性的螺旋藻新品系,显著降低藻粉生产中干燥的能耗。[方法]以用于工厂化培植的钝顶螺旋藻ZJU0115为出发品系,用组织匀浆-离心沉降法制得其原生质球,并先以0.6%EMS处理30 min再用2.4 kGy的60Coγ射线辐照,经含0.02%黄原胶(xanthan gum)的Zarrouk’s培养液筛选、藻丝单体分离培养、藻泥持水率和胞外多糖(EPS)等检测及生产培植试验。[结果]获得了一株产量、蛋白质和多糖含量与ZJU0115相当,而藻泥持水率和EPS含量分别下降5.9%和29.7%的突变体,命名为ZJU0115(HD)。超微结构与随机扩增多态性DNA标记(random amplified polymorphic DNA,RAPD)分析结果显示,与其亲本ZJU0115相比,ZJU0115(HD)藻丝表面更光滑,可能为酸性多糖的乳白状粘附物也更少;ZJU0115(HD)细胞内的多磷酸盐颗粒显著变小且呈弥散状;基因组DNA在随机引物S90的扩增产物中显示出多态性差异。[结论]ZJU0115(HD)在工厂化培植中生产性状好、高沥水性能稳定,藻泥的干燥能耗降低了近50%,它的育成与应用,有助于推进当前螺旋藻产业迈向高效、节能、绿色、环保发展的新阶段。