The Impact of Arf1 on Hypoxia Signaling and Oral Cancer

Arf1 对缺氧信号传导和口腔癌的影响

• 批准号: 10422109
• 负责人: Yong Teng
• 金额: $ 8.25万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-08 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10422109
• 关键词: Impact; Arf1; Hypoxia; Signaling; Oral

PROJECT SUMMARY Oral squamous cell carcinoma (OSCC) remains a challenging clinical problem because of the persisting high rate of local and distant failure. Hypoxia is prevalent in OSCC and often provides a strong selective pressure for the most aggressive and metastatic tumors, which emphasize the need for better understanding of molecular mechanisms and regulators responsible for the acquisition of metastatic potential under hypoxic conditions. We now have data demonstrating that ADP-ribosylation factor 1 (Arf1), a hypoxia-responsive trafficking protein, is required and sufficient to hypoxia-induced OSCC invasion and metastasis. The aberrant overexpression and hyperactivation of Arf1 leads to increased invasion potential upon hypoxia, raising the possibility to develop novel regimens by targeting Arf1 in order to eventually increase cure rate in OSCC. Our overarching goal is to improve the survival of patients with OSCC by revealing the functional consequences of Arf1 dysfunction under hypoxia and understanding the underlying mechanisms. There are two aims in the proposal to test our hypothesis. Aim 1 is to dissect the cooperatively transcriptional and epigenetic regulation in hypoxia-induced Arf1 upregulation. Aim 2 is to Illustrate the molecular mechanism and the functional consequences of hypoxia-induced Arf1 hyperactivation. These pilot studies will provide a solid rationale for a more comprehensive investigation into the regulation and role of Arf1 in hypoxic OSCC for which future R01 mechanism support will be sought. Overall, our studies will gain mechanistic insight into hypoxia-induced OSCC metastasis by exploring Arf1 as a novel druggable target for hypoxic tumors, and build a foundation for Arf1-targeted anticancer therapeutic modality. This project would directly impact the future development of prognostic variables and treatment strategies for OSCC, especially for those tumors in hypoxic microenvironment.

项目摘要 口服鳞状细胞癌（OSCC）仍然是一个具有挑战性的临床问题，因为 持续的局部和遥远失败率持续存在。缺氧在OSCC中很普遍，并且经常 为最具侵略性和转移性肿瘤提供了强大的选择压力， 强调需要更好地理解分子机制和调节剂 负责在低氧条件下获取转移潜力。我们现在有 数据表明ADP-核糖基化因子1（ARF1），一种缺氧反应性贩运 蛋白质是需要蛋白质，足以足以缺氧诱导的OSCC侵袭和转移。这 ARF1的异常过表达和过度激活导致侵袭潜力增加 缺氧，通过靶向ARF1来提高开发新方案的可能性，以最终 增加OSCC的治愈率。我们的总体目标是提高患者的生存 OSCC通过在缺氧和 了解基本机制。提案中有两个目标来测试我们 假设。目的1是剖析合作的转录和表观遗传调节 缺氧引起的ARF1上调。目标2是说明分子机制和 缺氧诱导的ARF1过度激活的功能后果。这些试点研究将 为对调节和作用进行更全面的调查提供了坚实的理由 在低氧OSCC中，将寻求R01机制支持的ARF1。总体而言，我们的 研究将通过探索ARF1作为缺氧诱导的OSCC转移的机械洞察力。 一个新型的可吸毒靶标的缺氧肿瘤，并为ARF1靶向抗癌的基础奠定了基础 治疗方式。该项目将直接影响预后的未来发展 OSCC的变量和治疗策略，特别是对于那些缺氧的肿瘤 微环境。

项目成果

Pyroptosis at the forefront of anticancer immunity.

• DOI: 10.1186/s13046-021-02065-8
• 发表时间: 2021-08-24
• 期刊: Journal of experimental & clinical cancer research : CR
• 作者: Loveless R;Bloomquist R;Teng Y
• 通讯作者: Teng Y

Iron, Ferroptosis, and Head and Neck Cancer.

• DOI: 10.3390/ijms242015127
• 发表时间: 2023-10-12
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Teng Y;Gao L;Mäkitie AA;Florek E;Czarnywojtek A;Saba NF;Ferlito A
• 通讯作者: Ferlito A

Targeting WASF3 Signaling in Metastatic Cancer.

• DOI: 10.3390/ijms22020836
• 发表时间: 2021-01-15
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Loveless R;Teng Y
• 通讯作者: Teng Y

Visualizing and Evaluating Cancer Cell Growth and Invasion by a Novel 3D Culture System.

• DOI: 10.1007/978-1-0716-0471-7_9
• 发表时间: 2020
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Shay C;Lang L;Teng Y
• 通讯作者: Teng Y

ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development.

• DOI: 10.1186/s13046-022-02274-9
• 发表时间: 2022-01-29
• 期刊: Journal of experimental & clinical cancer research : CR
• 作者: Lang L;Loveless R;Dou J;Lam T;Chen A;Wang F;Sun L;Juarez J;Qin ZS;Saba NF;Shay C;Teng Y
• 通讯作者: Teng Y