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更新于：2025-05-07

FOXK2

更新于：2025-05-07

基本信息

别名

forkhead box K2、Forkhead box protein K2、FOXK2

+ [5]

简介

Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (By similarity). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:22083952, PubMed:25451922). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK2-bound genes (PubMed:24634419, PubMed:30664650).

关联

项与 FOXK2 相关的药物

CN114907319

专利挖掘

靶点

FOXK2

作用机制-

在研机构

华创合成制药股份有限公司

原研机构

华创合成制药股份有限公司

在研适应症

真菌病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 FOXK2 相关的临床结果

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100 项与 FOXK2 相关的转化医学

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0 项与 FOXK2 相关的专利（医药）

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147

项与 FOXK2 相关的文献（医药）

2025-05-01·International Journal of Biological Macromolecules

C15orf39, a downstream effector of PI3K/AKT signaling, promotes gastric carcinogenesis and correlates with patient outcomes

Article

作者: Yu, Jiahua ; Hu, Qingqing ; Fan, Kailing ; Gao, Yong ; Li, Yandong

The phosphatidylinositol-3-kinases (PI3K) signaling pathway is highly complex and well-known to exert oncogenic roles in multiple cancer types. Exploring new factors involved in this pathway may offer the potential for improving the early diagnosis and treatment strategies for cancers. Here we used gastric cancer (GC) as a model to identify co-regulated effectors downstream of three catalytic subunits of PI3K through high-throughput sequencing in PIK3CA, PIK3CB, and PIK3CD knockdown GC cells. C15orf39, a new uncharacterized gene, was selected due to the most significant expression change. qRT-PCR and immunohistochemistry analyses revealed that C15orf39 was frequently upregulated in GC tissues and strongly correlated with poor clinical outcomes in GC patients. Gain- and loss-of-function studies demonstrated that C15orf39 promoted GC cell proliferation, migration, and drug resistance. Mechanistically, C15orf39 promoted GC progression possibly via modulating cell mitosis and cell cycle. FOXK2, a transcription factor activated by PI3K/AKT signaling, could bind to the promoter of C15orf39 and positively regulate C15orf39 expression. These findings unveiled a new PI3K/AKT/FOXK2/C15orf39 signaling axis that promotes GC development and progression. C15orf39 may become a potential biomarker for early diagnosis and personalized treatment to improve the prognosis of GC patients.

2025-02-25·Proceedings of the National Academy of Sciences

A circRNA–mRNA pairing mechanism regulates tumor growth and endocrine therapy resistance in ER-positive breast cancer

Article

作者: Liu, Wen ; Zhang, Yue-ying ; Du, Jiao ; Wen, Xiao-sha ; He, Hua ; Hu, Guo-sheng ; Yi, Jia ; Nie, Rui-chao ; Chen, Xue ; Wang, Lei ; Luo, Di-xian ; Chen, Shang

The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and drug resistance remain incompletely understood. Elevated expression of CCND1 is linked to enhanced invasiveness, poorer prognosis, and resistance to drug therapies in ER-positive breast cancer. In this study, we identify a highly expressed circular RNA (circRNA) derived from FOXK2 , called circFOXK2, which plays a key role in stabilizing CCND1 mRNA, thereby promoting cell cycle progression, cell growth, and endocrine therapy resistance in ER-positive breast cancer cells. Mechanistically, circFOXK2 binds directly to CCND1 mRNA via RNA–RNA pairing and recruits the RNA-binding protein ELAVL1/HuR, stabilizing the CCND1 mRNA and enhancing CCND1 protein levels. This results in activation of the CCND1–CDK4/6–p-RB–E2F signaling axis, driving the transcription of downstream E2F target genes and facilitating the G1/S transition during cell cycle progression. Notably, targeting circFOXK2 with antisense oligonucleotide (ASO-circFOXK2) suppresses ER-positive breast cancer cell growth both in vitro and in vivo. Moreover, combination therapy with ASO-circFOXK2 and tamoxifen exhibits synergistic effects and restores tamoxifen sensitivity in tamoxifen-resistant cells. Clinically, high circFOXK2 expression is positively correlated with CCND1 levels in both ER-positive breast cancer cell lines and patient tumor tissues. Overall, our findings reveal the critical role of circFOXK2 in stabilizing the oncogene CCND1 and promoting cancer progression, positioning circFOXK2 as a potential therapeutic target for ER-positive breast cancer in clinical settings.

2025-01-01·Journal of Cellular and Molecular Medicine

Foxk2 Enhances Adipogenic Differentiation by Relying on the Transcriptional Activation of Peroxisome Proliferator‐Activated Receptor Gamma

Article

作者: Li, Yachong ; Zhang, Shan ; Zhu, Endong ; Zhou, Jie ; You, Yanru ; Wang, Baoli ; Zhen, Ruonan ; Li, Mingcong ; Yuan, Hairui ; Liu, Ying ; Li, Ran

ABSTRACTProper differentiation of bone marrow stromal cells (BMSCs) into adipocytes is crucial for maintaining skeletal homeostasis. However, the underlying regulatory mechanisms remain incompletely understood, posing a challenge for the treatment of age‐related osteopenia and osteoporosis. Here, through comprehensive gene expression analysis during BMSC differentiation into adipocytes, we identified the forkhead transcription factor Foxk2 as a key regulator of this process. Foxk2 expression was significantly higher in the inguinal and epididymal white adipose tissues of db/db mice compared to non‐obese db/m controls and was induced in BMSCs, C3H/10 T1/2, and ST2 cells following adipogenic stimulation. Overexpression of Foxk2 promoted adipogenic differentiation of C3H/10 T1/2, ST2, and BMSCs, accompanied by increased expression of lipogenic factors. Conversely, Foxk2 silencing inhibited adipogenic differentiation. Moreover, Foxk2 also facilitated lipogenesis of C3H/10 T1/2 and ST2 cells. Adipogenic stimuli triggered the nuclear translocation of Foxk2 through PI3‐kinase and mTOR signalling pathways. Once in the nucleus, Foxk2 is directly bound to the promoters of Pparγ1 and Pparγ2, thereby enhancing their transcriptional activity. Notably, PPARγ1 and PPARγ2 reciprocally augmented the transcriptional activity of the Foxk2 promoter, indicating the presence of a Foxk2‐PPARγ positive feedback loop that drives adipogenesis.

项与 FOXK2 相关的新闻（医药）

2024-12-08

·ioncology

SABCS 2024丨盛幕将启，中国专家入选壁报展示（Poster Session 5上）

编者按：第47届圣安东尼奥乳腺癌研讨会（SABCS）将于当地时间2024年12月10日至13日在美国得克萨斯州圣安东尼奥举行。SABCS是全球最大的乳腺癌领域盛会，来自102个国家的超过1万名注册参会者将在为期四天的会议中展示1886篇被接受的论文摘要。肿瘤瞭望特别整理中国专家被收录的壁报内容，以飨读者。（注：因官网未公布详细作者单位，如有遗漏或错误，欢迎留言指正。）为深度报道此次盛会，《肿瘤瞭望》特此开设“瞭望联播”专栏，并荣幸邀请到江苏省人民医院殷咏梅教授担任特邀观察员。在会议期间，殷教授将连线SABCS现场的中国专家——复旦大学附属肿瘤医院张剑教授、浙江大学医学院附属第一医院傅佩芬教授、复旦大学附属肿瘤医院李俊杰教授、中山大学孙逸仙纪念医院刘强教授（按预计连线日期排序），每日实时传递会议的重磅研究成果与亮点发现。诚邀各位读者密切关注“瞭望联播”和《肿瘤瞭望》推出的栏目，共同见证SABCS大会的最新前沿进展，洞悉乳腺癌研究领域的未来趋势！ Poster Session 5 日期：12月13日时间：12:30～2:00 p.m. 地点：Halls 2-3 P5-01-04: Determination and clinical characteristics of bone pseudoprogression on advanced first-line therapy in metastatic breast cancer 转移性乳腺癌一线治疗中骨假性进展的确定和临床特征报告作者：Yuan Yuan P5-01-05: Clinicopathological features and outcomes of ERlow/HER2-low expression in de novo metastatic breast cancer: a preliminary cohort study 初发转移性乳腺癌ER低表达/ HER2低表达的临床病理特征和预后：一项初步队列研究报告作者：Chongxi Ren P5-01-16: m6A reader YTHDF3 promotes epithelial-mesenchymal transition and metastasis through facilitating Notch2 translation in breast cancer m6A解读器YTHDF3通过促进Notch2翻译促进乳腺癌上皮-间质转化和转移报告作者：Hong-Yu Chen P5-01-24: PPFIA4 mediates glucose metabolism reprogramming to alter the biological characteristics of breast cancer PPFIA4通过介导糖代谢重编程改变乳腺癌的生物学特性报告作者：Haochen Yu P5-01-25: Romidepsin Targets HDAC1/2 to Induce Ferroptosis in TNBC Enhancing Chemosensitivity to Eribulin Romidepsin靶向HDAC1/2诱导TNBC的铁死亡增强对艾立布林的化疗敏感性报告作者：Weipeng ZHAO P5-01-29: Development of a Novel Antigen Presentation Assay in Triple-negative Breast Cancer 三阴性乳腺癌新型抗原呈递检测方法的开发报告作者：Mei Li P5-02-24: Targeting FOXK2 signaling in breast cancers with FOXK2 amplification/overexpression and PIK3CA oncogenic mutations: a promising therapeutic strategy? 靶向FOXK2信号通路在具有FOXK2扩增/过表达和PIK3CA致癌突变的乳腺癌：一个有前景的治疗策略？报告作者：Hong Zhang P5-03-13: Trastuzumab emtansine versus disitamab vedotin for HER2-positive metastatic breast cancer: a multicenter retrospective real-world study 比较恩美曲妥珠单抗与维迪西妥单抗治疗HER2阳性转移性乳腺癌：一项多中心回顾性真实世界研究报告作者：Huihui Li P5-03-14: Efficacy and safety of inetetamab-containing regimens in patients with HER2-positive metastatic breast cancer in firstline/second-line setting 含inetetamab方案在HER2阳性转移性乳腺癌患者一线/二线治疗中的疗效和安全性报告作者：Yuxin Mu P5-03-25: Trastuzumab deruxtecan (T-DXd) in leptomeningeal metastases from HER2-altered cancers T-DXd治疗HER2突变癌症患者的软脑膜转移报告作者：Qian Ma P5-03-27: Updated Real-World Evidence on the Efficacy and Safety of Inetetamab-Based Therapy in HER2-Positive Metastatic Breast Cancer Patients Previously Treated with Trastuzumab 基于inetetamab治疗曲妥珠单抗治疗过的HER2阳性转移性乳腺癌患者有效性和安全性的最新真实世界证据报告作者：Yangyang Duan P5-04-16: Stromal tumor-infiltrating lymphocytes-based model predicts efficacy for neoadjuvant therapy in HER2-low early breast cancer 基于间质瘤浸润淋巴细胞的模型预测HER2低表达早期乳腺癌新辅助治疗的疗效报告作者：Zhuxi Duan P5-04-18: Clinical Validation of an Ultra-Sensitive ctDNA NGS Assay in HR-Positive, HER2-Negative Breast Cancer Patients 超敏感ctDNA NGS检测在HR阳性/HER2阴性乳腺癌患者中的临床验证报告作者：Haoran Tang P5-04-22: Prognostic value of circulating tumor DNA (ctDNA) in early triple-negative breast cancer (TNBC): A systematic review and meta-analysis 循环肿瘤DNA（ctDNA）在早期三阴性乳腺癌（TNBC）中的预后价值：一项系统综述和荟萃分析报告作者：Diana Zhang P5-04-25: Detection of Human Epidermal Growth Factor Receptor 2 (HER2) in Cultured Circulating Tumor Cells (CTCs) Isolated from Peripheral Blood of Breast Cancer Patients 从乳腺癌患者外周血分离培养的循环肿瘤细胞（ctc）中人类表皮生长因子受体2 （HER2）的检测报告作者：Ying Chang P5-04-26: Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study 应用仅肿瘤靶向测序的924例台湾乳腺癌检测中BRCA1、BRCA2和PALB2基因组改变的患病率：来自VGH-TAYLOR研究的扩展数据分析报告作者：Han Fang Cheng P5-05-02: Pharmacokinetic profile and preliminary efficacy of GQ1001, a next generation HER2-targeting ADC, combined with pyrotinib in pretreated patients with HER2-positive metastatic breast cancer: A phase 1b clinical trial 下一代靶向HER2的ADC GQ1001联合吡咯替尼治疗既往接受过治疗的HER2阳性转移性乳腺癌患者的药代动力学特征和初步疗效：一项1b期临床试验报告作者：Biyun Wang P5-05-07: A prospective, multicenter, single-arm clinical study of inetetamab combined with pyrotinib and capecitabine/vinorelbine in the treatment of HER2-positive metastatic breast cancer resistant to previous trastuzumab treatment inetetamab联合吡咯替尼和卡培他滨/长春瑞滨治疗曲妥珠单抗耐药的HER2阳性转移性乳腺癌的前瞻性、多中心、单臂临床研究报告作者：Yan Xue P5-05-08: Inetetamab-base regimens for patients with HER2- positive metastatic breast cancer and brain metastases: a realworld retrospective study 以inetetamab为基础的方案治疗HER2阳性转移性乳腺癌和脑转移患者：一项真实世界回顾性研究报告作者：Liping Chen P5-05-09: Trastuzumab deruxtecan combined with pyrotinib in first-line HER2-positive unresectable or metastatic breast cancer: an exploratory, multi-center, single-arm, phase Ib/II study (TROPHY) 德曲妥珠单抗联合吡咯替尼一线治疗HER2阳性不可切除或转移性乳腺癌：一项探索性、多中心、单组、Ib/II期研究（TROPHY）报告作者：Ying Fan P5-05-12: Real-world outcome of patients with HER2-positive metastatic breast cancer who were treated with inetetamabcontaining regimens: A multicenter retrospective analysis conducted in China 含inetetamab方案治疗HER2阳性转移性乳腺癌患者的真实世界结局：一项中国多中心回顾性分析报告作者：Huihui Li P5-05-14: Real-World Treatment Patterns and Clinical Outcomes of Inetetamab combined with pyrotinib plus chemotherapy in Her-2 negative metastatic breast cancer patients : a multi-center retrospective study HER2阴性转移性乳腺癌患者Inetetamab联合吡咯替尼联合化疗的真实世界治疗模式和临床结局：一项多中心回顾性研究报告作者：Huanhuan Zhou P5-05-16: Real-world analysis of inetetamab-based therapy for the treatment of HER2-positive advanced breast cancer. 基于inetetamab治疗HER2阳性晚期乳腺癌的真实世界分析报告作者：Cailing Lin P5-05-17: Trastuzumab deruxtecan for HER2-positive and HER2- low breast cancer brain metastasis: Results from a singleinstitution retrospective study. 德曲妥珠单抗治疗HER2阳性和HER2低表达的乳腺癌脑转移：一项单机构回顾性研究结果报告作者：Chunfang Hao P5-05-22: ARX788 for patients with HER2-positive advanced breast cancer: characterization, time course, and monitoring and management of adverse event from the phase III ACE-Breast-02 study ARX788治疗HER2阳性晚期乳腺癌患者：ACE-Breast-02 III期研究的特征、时间进程以及不良事件的监测和管理报告作者：Jian Zhang P5-05-24: RC48-ADC (Disitamab vedotin, a HER2-directed antibody-drug conjugate) in Combination with Pyrotinib for Trastuzumab-treated HER2-Positive Recurrent or Metastatic Breast Cancer: A Phase Ib/II Study RC48-ADC （Diitamab vedotin，一种靶向HER2的抗体-药物偶联物）联合吡咯替尼治疗曲妥珠单抗经治的HER2阳性复发或转移性乳腺癌：一项Ib/II期研究报告作者：Xinrui Liang P5-05-29: Real-world efficacy and safety of inetetamab-based therapy in patients with HER2- positive metastatic breast cancer with prior trastuzumab exposure: A prospective real-world study 在曲妥珠单抗暴露的HER2阳性转移性乳腺癌患者中，基于inetetamab的治疗的真实世界疗效和安全性：一项前瞻性真实世界研究报告作者：Dedian Chen （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

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