Drosophila APC as a Model for Cytoskeletal Regulation and Cancer Biology

果蝇 APC 作为细胞骨架调节和癌症生物学的模型

• 批准号: 8325247
• 负责人: John Shaw Poulton
• 金额: $ 5.13万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-17 至 2012-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325247
• 关键词: APC2 gene; Actins; Address; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Attention; Cancer Biology; Cell physiology; Chromosomal Instability; Colon Carcinoma; Cytoskeletal Modeling; Cytoskeleton; Defect; Development; Developmental Process; Drosophila genus; Event; Kinetochores; Link; Malignant Neoplasms; Microtubules; Mitotic spindle; Mutation; Oncogenic; Prevention; Process; Proteins; Regulation; Research; Role; Series; Signal Transduction; Testing; Tumor Suppressor Proteins; Work; base; cancer initiation; carcinogenesis; improved; protein complex; protein function; public health relevance; stem; tumor progression; tumorigenesis; APC2 gene; Actins; Address; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Attention; Cancer Biology; Cell physiology; Chromosomal Instability; Colon Carcinoma; Cytoskeletal Modeling; Cytoskeleton; Defect; Development; Developmental Process; Drosophila genus; Event; Kinetochores; Link; Malignant Neoplasms; Microtubules; Mitotic spindle; Mutation; Oncogenic; Prevention; Process; Proteins; Regulation; Research; Role; Series; Signal Transduction; Testing; Tumor Suppressor Proteins; Work; base; cancer initiation; carcinogenesis; improved; protein complex; protein function; public health relevance; stem; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): Adenomatous Polyposis Coli (APC) proteins are tumor suppressors known for their roles in Wnt signaling and cytoskeletal regulation. APC proteins function in many developmental processes and mutations in APC are present in ~80% of colon cancers. Recent research identified important cytoskeletal functions of APC including regulating mitotic spindle orientation, spindle attachment, and prevention of chromosomal instability. Because defects in these cytoskeletal processes are potentially oncogenic, the dual roles of APC in Wnt and cytoskeleton regulation may underlie APC's significance as a tumor suppressor. The mechanisms by which APC regulates the cytoskeleton remain unclear. We hypothesize they are based on APC localization and its interaction with microtubules, the actin cytoskeleton, and other cytoskeletal regulators. To further our understanding of APC in cytoskeletal regulation I will use Drosophila APC to address a series of key questions. Which regions of the APC protein participate in its cytoskeletal functions? Is APC function in Wnt signaling related to its cytoskeletal roles? Is localization of APC important for its cytoskeletal functions? What are the relevant partners of APC in regulating the cytoskeleton? Answering these questions will provide a more complete understanding of APC's role in both normal development and cancer. PUBLIC HEALTH RELEVANCE: Mutations in Adenomatous Polyposis Coli (APC) are responsible for approximately 80% of colon cancers, and APC mutations have also been associated with several other forms of cancer. Elucidating the mechanisms by which APC proteins regulate important cellular processes and identifying APCs relevant protein partners should greatly improve our understanding of APCs role in cancer biology.

描述（由申请人提供）：腺瘤性息肉病（APC）蛋白是肿瘤抑制剂，以其在Wnt信号传导和细胞骨架调节中的作用而闻名。 APC蛋白在许多发育过程中的功能，APC中的突变存在于大约80％的结肠癌中。最近的研究确定了APC的重要细胞骨架功能，包括调节有丝分裂的纺锤体方向，纺锤体附着和预防染色体不稳定性。由于这些细胞骨架过程中的缺陷可能具有致癌性，因此APC在WNT和细胞骨架调节中的双重作用可能是APC作为肿瘤抑制剂的重要性。 APC调节细胞骨架的机制尚不清楚。我们假设它们基于APC定位及其与微管，肌动蛋白细胞骨架和其他细胞骨架调节剂的相互作用。为了进一步了解细胞骨架调节中APC，我将使用果蝇APC解决一系列关键问题。 APC蛋白的哪些区域参与其细胞骨架功能？ Wnt信号中的APC功能与其细胞骨架角色有关吗？ APC的定位对其细胞骨架功能重要吗？ APC在调节细胞骨架时的相关伙伴是什么？回答这些问题将对APC在正常发育和癌症中的作用有更全面的了解。 公共卫生相关性：腺瘤性息肉病（APC）的突变是大约80％的结肠癌，APC突变也与其他几种形式的癌症有关。阐明APC蛋白调节重要细胞过程并鉴定APC相关蛋白伴侣的机制应大大提高我们对APC在癌症生物学中的作用的理解。