Tanaka Miwa, Nakamura Takuro
Division of Cancer Epigenomics, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Department of Experimental Pathology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Cancer Sci. 2025 Jul;116(7):1815-1822. doi: 10.1111/cas.70096. Epub 2025 May 4.
Crosstalk between cancer cells and the tumor microenvironment (TME) is a key event in malignant progression and metastasis. The secretion of bioactive substances by cancer cells remodels the TME, affecting the activities of its components, including blood vessels, mesenchymal cells, and immune cells. These substances are effectively delivered through intracellular trafficking and exocytosis of cytoplasmic vesicles. The small guanosine triphosphatase (GTPase) RAB27 and its effectors, synaptotagmin-like (SYTL) family proteins, play essential roles in vesicle trafficking. Our recent research demonstrates the upregulation of RAB27A/B and SYTL1/2 in alveolar soft part sarcoma and acute myeloid leukemia. This enhanced trafficking promotes angiogenesis and the occupation of leukemia cells in the bone marrow niche. This review focuses on the role of the RAB27/SYTL axis in various cancer types associated with TME modifications, with a discussion on its importance as a therapeutic target.
癌细胞与肿瘤微环境（TME）之间的串扰是恶性进展和转移中的关键事件。癌细胞分泌的生物活性物质重塑了肿瘤微环境，影响其组成部分的活性，包括血管、间充质细胞和免疫细胞。这些物质通过细胞质囊泡的细胞内运输和胞吐作用有效地传递。小GTP酶（GTPase）RAB27及其效应器，即类突触结合蛋白（SYTL）家族蛋白，在囊泡运输中起重要作用。我们最近的研究表明，RAB27A/B和SYTL1/2在肺泡软组织肉瘤和急性髓系白血病中上调。这种增强的运输促进了血管生成以及白血病细胞在骨髓微环境中的占据。本综述重点关注RAB27/SYTL轴在与肿瘤微环境改变相关的各种癌症类型中的作用，并讨论其作为治疗靶点的重要性。
