【第66期】前沿靶點速遞：每周醫(yī)學研究精選
日期：2025-12-03 14:27:09
01、靶點：TMEM16F/ANO6
應用：腫瘤免疫治療
來源：TMEM16F phospholipid scramblase regulates tumorigenesis by modulating the tumor immune microenvironment.Proc Natl Acad Sci U S A,2025 Oct 21
02、靶點：METTL5
應用：卵巢癌等的治療
來源：Tumor-Intrinsic METTL5 Modulates ATF4 Translation to Prevent T Cell-Induced Ferroptosis in Ovarian Cancer.Adv Sci (Weinh),2025 Oct 03
03、靶點：ZNF296
應用：腫瘤免疫逃逸機制研究
來源：ZNF296 Drives Immune Evasion in Epithelial Cancers by Repressing Immune Stimulatory Genes.Cancer Res,2025 Sep 24
04、靶點：G6PT/G6PC1
應用：糖原貯積癥Ib型的核心研究靶點
來源：Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.Nat Commun,2025 Oct 24
05、靶點：ANKRD55
應用：治療多發(fā)性硬化（MS）
來源：ANKRD55 is a key regulator of T cell inflammation in multiple sclerosis.J Clin Invest,2025 Oct 15
06、靶點：Nestin
應用：治療與干細胞衰老和功能障礙相關(guān)的退行性疾病
來源：Mitochondria-localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.Adv Sci (Weinh),2025 Sep 24
07、靶點：FBLN7
應用：代謝綜合征的新靶點
來源：Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.Protein Cell,2025 Oct 23
推薦產(chǎn)品
參考文獻
[1]TMEM16F phospholipid scramblase regulates tumorigenesis by modulating the tumor immune microenvironment.Proc Natl Acad Sci U S A,2025 Oct 21
[2]Tumor-Intrinsic METTL5 Modulates ATF4 Translation to Prevent T Cell-Induced Ferroptosis in Ovarian Cancer.Adv Sci (Weinh),2025 Oct 03
[3]ZNF296 Drives Immune Evasion in Epithelial Cancers by Repressing Immune Stimulatory Genes.Cancer Res,2025 Sep 24
[4]Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.Nat Commun,2025 Oct 24
[5]ANKRD55 is a key regulator of T cell inflammation in multiple sclerosis.J Clin Invest,2025 Oct 15
[6]Mitochondria-localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.Adv Sci (Weinh),2025 Sep 24
[7]Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.Protein Cell,2025 Oct 23
*免責聲明：華美生物內(nèi)容團隊僅是分享和解讀公開研究論文及其發(fā)現(xiàn)，本文僅作信息交流，文中觀點不代表華美生物立場，請理解。
應用：腫瘤免疫治療
來源：TMEM16F phospholipid scramblase regulates tumorigenesis by modulating the tumor immune microenvironment.Proc Natl Acad Sci U S A,2025 Oct 21
圖源：10.1073/pnas.2513910122[1]
深圳灣實驗室張洋團隊PNAS報道，鈣激活磷脂翻轉(zhuǎn)酶TMEM16F驅(qū)動腫瘤細胞非凋亡性PS外翻，經(jīng)“PS-AXL”信號誘導巨噬細胞M2極化、TGF-β1分泌及Treg擴增，抑制CD8+ T/NK功能。敲除TMEM16F或用小分子抑制劑阻斷該軸，可系統(tǒng)性重編程免疫微環(huán)境、引流淋巴結(jié)及脾臟，使M1/Tc/NK浸潤增加、MDSC/Treg減少，顯著抑制結(jié)直腸癌與黑色素瘤生長，且巨噬細胞缺失時抑瘤效應完全消失，證實其為核心靶細胞。研究確立TMEM16F-PS為保守免疫逃逸新機制，提供靶向上游翻轉(zhuǎn)酶以增強免疫治療響應的可轉(zhuǎn)化策略。02、靶點：METTL5
應用：卵巢癌等的治療
來源：Tumor-Intrinsic METTL5 Modulates ATF4 Translation to Prevent T Cell-Induced Ferroptosis in Ovarian Cancer.Adv Sci (Weinh),2025 Oct 03
圖源：10.1002/advs.202507718[2]
Weiyi Peng/Amir Jazaeri/何川團隊聯(lián)合在Adv Sci報道，核糖體甲基轉(zhuǎn)移酶METTL5通過催化18S rRNA m6A修飾選擇性促進ATF4翻譯，維持SLC7A11/SLC3A2抗氧化軸，阻斷T細胞誘導的鐵死亡；多模型CRISPR篩選及臨床隊列證實METTL5高表達與卵巢癌ICB耐藥和“免疫冷”微環(huán)境相關(guān)，抑制METTL5可重編程谷胱甘肽代謝、升高脂質(zhì)過氧化，使腫瘤對ICB敏感，提出METTL5-ATF4-鐵死亡軸為免疫聯(lián)合治療新靶點。03、靶點：ZNF296
應用：腫瘤免疫逃逸機制研究
來源：ZNF296 Drives Immune Evasion in Epithelial Cancers by Repressing Immune Stimulatory Genes.Cancer Res,2025 Sep 24
圖源：10.1158/0008-5472.CAN-25-0153[3]
潘登/曾澤賢團隊Cancer Research發(fā)文，利用CRISPRa篩選發(fā)現(xiàn)胚胎轉(zhuǎn)錄因子ZNF296在上皮腫瘤中高表達，通過招募NuRD復合物抑制FAS、ICAM1、CD58等免疫刺激基因，同時阻斷間質(zhì)程序，使腫瘤逃避免疫殺傷；敲除ZNF296或低劑量HDAC1抑制劑羅米地辛可恢復NK/T細胞毒性，提示ZNF296為免疫逃逸關(guān)鍵驅(qū)動因子和HDAC抑制劑療效預測標志物。04、靶點：G6PT/G6PC1
應用：糖原貯積癥Ib型的核心研究靶點
來源：Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.Nat Commun,2025 Oct 24
圖源：10.1038/s41467-025-64464-1[4]
姜道華/陳立功團隊合作在Nat Commun首次解析人源葡萄糖-6-磷酸轉(zhuǎn)運蛋白G6PT在空載、底物G6P結(jié)合及抑制劑綠原酸CHA結(jié)合下的高分辨冷凍電鏡結(jié)構(gòu)，揭示G6P通過“磷酸-葡萄糖雙亞位點”被識別，CHA則同時占據(jù)底物口袋并鎖固轉(zhuǎn)運蛋白于內(nèi)向閉塞構(gòu)象而雙重阻斷轉(zhuǎn)運；研究還將GSD-Ib致病突變定位至結(jié)構(gòu)，闡明其對構(gòu)象或底物結(jié)合的影響，為糖原貯積癥及代謝病藥物開發(fā)奠定結(jié)構(gòu)基礎(chǔ)。05、靶點：ANKRD55
應用：治療多發(fā)性硬化（MS）
來源：ANKRD55 is a key regulator of T cell inflammation in multiple sclerosis.J Clin Invest,2025 Oct 15
圖源：10.1172/JCI195214[5]
張存金團隊JCI報道，MS急性期未知蛋白ANKRD55在患者CD4?T細胞顯著上調(diào)；構(gòu)建ANKRD5缺失EAE模型顯示疾病減輕，TH1/TH17分化受抑。機制上，ANKRD55與CCT分子伴侶復合物互作并調(diào)控免疫突觸微管極化，放大TCR信號。靶向ANKRD55可阻斷T細胞初始激活，為MS急性期提供全新干預靶點。06、靶點：Nestin
應用：治療與干細胞衰老和功能障礙相關(guān)的退行性疾病
來源：Mitochondria-localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.Adv Sci (Weinh),2025 Sep 24
圖源：10.1002/advs.202507759[6]
項鵬/汪建成/車斯堯團隊Adv Sci報道，MSC標志蛋白Nestin經(jīng)TOM20導入線粒體膜間隙，與嵴維持蛋白Mic60互作，充當“線粒體骨架”穩(wěn)定嵴結(jié)構(gòu)，保障氧化磷酸化；缺失該定位致嵴崩解、能量衰竭及MSC早衰，而回補Nestin Tail3片段可重塑嵴并逆轉(zhuǎn)衰老，揭示線粒體Nestin-Mic60軸為延緩干細胞衰老與退行性疾病的新靶點。07、靶點：FBLN7
應用：代謝綜合征的新靶點
來源：Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.Protein Cell,2025 Oct 23
圖源：10.1093/procel/pwaf084[7]
胡承/嚴婧/張健團隊Protein & Cell發(fā)文：單細胞測序發(fā)現(xiàn)脂肪祖細胞（ASPC）特異高表達ECM蛋白FBLN7，肥胖時上調(diào)；構(gòu)建PDGFRα-Cre條件敲除小鼠顯示，F(xiàn)BLN7缺失通過阻斷其與TSP1結(jié)合及后續(xù)TGF-β激活，打破FBLN7-TSP1-TGFβ-Smad正反饋環(huán)，顯著減輕脂肪纖維化并改善糖脂代謝，靶向FBLN7中和抗體可復制保護效應，為代謝綜合征提供新干預靶點。推薦產(chǎn)品
| 靶點 | 重組蛋白 | 貨號 |
| ANO6 | Recombinant Human Anoctamin-6 (ANO6), partial | CSB-MP679761HU |
| ANKRD55 | Recombinant Human Ankyrin repeat domain-containing protein 55 (ANKRD55) | CSB-MP660753HU |
| FBLN7 | Recombinant Human Fibulin-7 (FBLN7) | CSB-EP687502HU |
| G6PC1 | Recombinant Human Glucose-6-phosphatase (G6PC), partial | CSB-YP009118HU1 |
| METTL5 | Recombinant Human Methyltransferase-like protein 5 (METTL5) | CSB-MP873639HU |
| NES | Recombinant Human Nestin (NES), partial | CSB-YP015713HU |
| ZNF296 | Recombinant Human Zinc finger protein 296 (ZNF296) | CSB-MP026648HU |
參考文獻
[1]TMEM16F phospholipid scramblase regulates tumorigenesis by modulating the tumor immune microenvironment.Proc Natl Acad Sci U S A,2025 Oct 21
[2]Tumor-Intrinsic METTL5 Modulates ATF4 Translation to Prevent T Cell-Induced Ferroptosis in Ovarian Cancer.Adv Sci (Weinh),2025 Oct 03
[3]ZNF296 Drives Immune Evasion in Epithelial Cancers by Repressing Immune Stimulatory Genes.Cancer Res,2025 Sep 24
[4]Structural basis for transport and inhibition of the human glucose-6-phosphate transporter G6PT.Nat Commun,2025 Oct 24
[5]ANKRD55 is a key regulator of T cell inflammation in multiple sclerosis.J Clin Invest,2025 Oct 15
[6]Mitochondria-localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.Adv Sci (Weinh),2025 Sep 24
[7]Fibulin-7 in progenitor cells promotes adipose tissue fibrosis and disrupts metabolic homeostasis in obesity.Protein Cell,2025 Oct 23
*免責聲明：華美生物內(nèi)容團隊僅是分享和解讀公開研究論文及其發(fā)現(xiàn)，本文僅作信息交流，文中觀點不代表華美生物立場，請理解。
