更新于：2024-05-01

FSTL3

follistatin like 3

更新于：2024-05-01

基本信息

别名

FLRG、follistatin like 3、Follistatin-like protein 3

+ [4]

简介

Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiationc. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10.

关联

项与 FSTL3 相关的药物

ELV-101

靶点

FSTL3

作用机制

FSTL3抑制剂

在研机构

Elevian, Inc.初创企业

原研机构

Elevian, Inc.初创企业

在研适应症

心血管疾病 [+1]

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 FSTL3 相关的临床结果

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100 项与 FSTL3 相关的转化医学

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0 项与 FSTL3 相关的专利（医药）

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290

项与 FSTL3 相关的文献（医药）

2024-02-01·Cell death & disease

FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer.

Article

作者: Haiyang Li ; Na Zheng ; Anning Guo ; Weiwei Tang ; Muxin Li ; Yuanyuan Cao ; Xinhua Ma ; Hongyong Cao ; Yong Ma ; Hanjin Wang ; Shuli Zhao

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354-406 amino acids) to suppress the latter's ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8⁺ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25⁺ Foxp3⁺) and exhausted T cells (PD1⁺ CD8⁺), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

2024-01-19·Journal of cancer research and clinical oncology

FSTL3 is associated with prognosis and immune cell infiltration in lung adenocarcinoma.

Article

作者: Xiangzhi Meng ; Xiaojian Zhao ; Boxuan Zhou ; Weijian Song ; Yicheng Liang ; Mei Liang ; Minjun Du ; Jianwei Shi ; Yushun Gao

PURPOSE:

FSTL3 expression is altered in various types of cancer. However, the role and mechanism of action of FSTL3 in lung adenocarcinoma development and tumor immunity are unknown. We investigated the association between FSTL3 expression and clinical characteristics and immune cell infiltration in lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) and a separate validation set from our hospital.

METHODS:

Data on immune system infiltration, gene expression, and relevant clinical information were obtained by analyzing lung adenocarcinoma sample data from TCGA database. Using online tools like GEPIA, the correlations between FSTL3 expression and prognosis, clinical stage, survival status, and tumor-infiltrating immune cells were examined. In a validation dataset, immunohistochemistry was performed to analyze FSTL3 expression and its related clinical characteristics.

RESULTS:

FSTL3 expression was markedly reduced in patients with lung adenocarcinoma. N stage, pathological stage, and overall survival were significantly correlated with FSTL3 expression. According to GSEA, FSTL3 is strongly linked to signaling pathways such as DNA replication and those involved in cell cycle regulation. Examination of TCGA database and TIMER online revealed a correlation between FSTL3 and B cell, T cell, NK cell, and neutrophil levels. The prognosis of patients with lung adenocarcinoma was significantly affected by six genes (KRT6A, VEGFC, KRT14, KRT17, SNORA12, and KRT81) related to FSTL3.

CONCLUSION:

FSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.

2024-01-15·Nature communications

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development.

Article

作者: Amil M Shah ; Peder L Myhre ; Victoria Arthur ; Pranav Dorbala ; Humaira Rasheed ; Leo F Buckley ; Brian Claggett ; Guning Liu ; Jianzhong Ma ; Ngoc Quynh Nguyen ; Kunihiro Matsushita ; Chiadi Ndumele ; Adrienne Tin ; Kristian Hveem ; Christian Jonasson ; Håvard Dalen ; Eric Boerwinkle ; Ron C Hoogeveen ; Christie Ballantyne ; Josef Coresh ; Torbjørn Omland ; Bing Yu

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.

项与 FSTL3 相关的新闻（医药）

2024-02-06

·今日头条

双重疗效！南医大学者发现促进肿瘤免疫逃避并减弱对抗 PD1 治疗反应的新靶点

本文为转化医学网原创，转载请注明出处作者：Sophia 导读：程序化细胞死亡1配体1（PDL1）/程序化细胞死亡1（PD1）阻断免疫疗法为结直肠癌（CRC）的治疗提供了前景性策略，但治疗效果的各种限制仍然存在。 2024年2月1日，南京医科大学附属南京市第一医院研究人员在期刊《Cell Death & Disease》上发表题为“FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer”的研究论文，研究揭示了 FSTL3 在 CRC 免疫逃避和 ICB 治疗耐药中的确切作用，这对于为那些对 ICB 治疗耐药的 CRC 患者寻找新的生物标志物和治疗途径至关重要。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-06469-0 研究背景 01 由于饮食习惯、肥胖和生活方式因素，结直肠癌（CRC）已成为全球发病率和死亡率最高的消化系统恶性肿瘤。导致CRC进展的过程涉及多个癌基因在不同阶段的突变积累，肿瘤植入的免疫微环境也发挥着关键的调节作用。由于免疫系统在疾病防御和监测中的关键作用，针对免疫系统的免疫治疗近年来已成为癌症治疗的前沿，为CRC的治疗开辟了新的途径。针对 CRC 的免疫治疗，免疫检查点阻断（ICB）表现出相当大的优势，它针对免疫检查点，如程序性细胞死亡1（PD1）、程序性细胞死亡1配体1（PDL1）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）。然而，微卫星不稳定高（MSI-H）患者占对 ICB 有反应的 CRC 患者的大多数，而 MSI-H 患者仅占所有 CRC 病例的约 15%。除此之外，微卫星不稳定性低（MSI-L）患者的大多数和50％的MSI-H患者表现出对ICB的抵抗力。据猜测，肿瘤抗原呈递不足、T细胞疲劳以及肿瘤微环境（TME）中的免疫抑制信号都有助于CRC中的ICB抵抗力。因此，充分了解癌细胞对免疫系统的防御和逃逸机制是必要的，这是探索可能对免疫治疗有响应的人群所需的潜在生物标志物和发现新的免疫治疗靶点的先决条件。 Follistatin-like 3（FSTL3）是由脂肪组织、生殖系统、胰腺、肝脏、骨骼肌和胎盘释放的分泌性糖蛋白[8]。除了调节睾丸衰老和生长外，FSTL3还参与调节葡萄糖和脂质代谢。已经发现FSTL3促进脂质积累和炎症细胞因子的释放，以及在泡沫细胞中触发CD36和脂氧合酶1的表达。FSTL3还被证明有助于肺癌、肾癌和胃癌的发展，并适用于作为一种新的不良生存标志物。根据一些研究，FSTL3在CRC组织中高度表达，并与CRC患者的不良预后相关。然而， FSTL3在CRC的免疫逃避和免疫治疗反应中的功能和机制仍不清楚。研究结果 02 根据先前的研究报告，类似于卵泡刺激素的3（FSTL3）可以通过诱导脂质积累在巨噬细胞中介导炎症反应。在此，我们揭示了FSTL3在CRC微环境中的恶性细胞中过度表达，特别是FSTL3的表达水平与肿瘤免疫逃逸和抗PD1治疗的临床疗效有关。进一步的研究确定了缺氧的肿瘤微环境通过HIF1α在CRC细胞中诱导FSTL3表达，FSTL3可以结合转录因子c-Myc（354-406氨基酸）来抑制后者的在免疫能力肿瘤模型中的结果验证了FSLT3在肿瘤细胞中的敲除增加了肿瘤微环境中CD8 T细胞的比例，减少了调节性T细胞（CD25 Foxp3）和疲劳T细胞（PD1 CD8）的比例，并协同提高了抗PD1治疗的疗效。总之， FSTL3增强了c-Myc介导的转录调控以促进免疫逃逸，并减弱了对CRC的抗PD1治疗反应，表明FSTL3作为免疫治疗效果的生物标志物以及CRC的新型免疫治疗靶点的潜力。泛素化并增加其稳定性，从而上调PDL1和吲哚醋酸2,3-二氧化酶1（IDO1）的表达。研究结论 03 总之，研究发现FSTL3不仅在CRC的癌细胞中高表达，而且与免疫逃逸有关。在癌细胞中，FSTL3通过与c-Myc的相互作用阻止了c-Myc的泛素化和降解，触发了下游PDL1和IDO1的转录表达，从而阻断了CD8 T细胞的抗肿瘤效应并增强了Tregs的浸润（图8D）。此外，FSTL3的高表达导致对抗PD1疗法的抵抗，可以通过与IDO1抑制剂的联合治疗逆转。 FSTL3在CRC微环境中的具体功能和机理示意图参考资料： https://www-nature-com.libproxy1.nus.edu.sg/articles/s41419-024-06469-0 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

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