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AXL受体酪氨酸激酶作为一个有前景的治疗靶点,主导癌症进展和转移的多个方面。

AXL Receptor Tyrosine Kinase as a Promising Therapeutic Target Directing Multiple Aspects of Cancer Progression and Metastasis.

作者信息

Goyette Marie-Anne, Côté Jean-François

机构信息

Montreal Clinical Research Institute (IRCM), Montréal, QC H2W 1R7, Canada.

Molecular Biology Programs, Université de Montréal, Montréal, QC H3T 1J4, Canada.

出版信息

Cancers (Basel). 2022 Jan 18;14(3):466. doi: 10.3390/cancers14030466.

Abstract

The receptor tyrosine kinase AXL is emerging as a key player in tumor progression and metastasis and its expression correlates with poor survival in a plethora of cancers. While studies have shown the benefits of AXL inhibition for the treatment of metastatic cancers, additional roles for AXL in cancer progression are still being explored. This review discusses recent advances in understanding AXL's functions in different tumor compartments including cancer, vascular, and immune cells. AXL is required at multiple steps of the metastatic cascade where its activation in cancer cells leads to EMT, invasion, survival, proliferation and therapy resistance. AXL activation in cancer cells and various stromal cells also results in tumor microenvironment deregulation, leading to modulation of angiogenesis, fibrosis, immune response and hypoxia. A better understanding of AXL's role in these processes could lead to new therapeutic approaches that would benefit patients suffering from metastatic diseases.

摘要

受体酪氨酸激酶AXL正在成为肿瘤进展和转移中的关键角色,其表达与多种癌症患者的不良生存率相关。虽然研究已表明抑制AXL对转移性癌症治疗有益,但AXL在癌症进展中的其他作用仍在探索中。本综述讨论了在理解AXL在不同肿瘤微环境(包括癌细胞、血管细胞和免疫细胞)中的功能方面的最新进展。AXL在转移级联反应的多个步骤中发挥作用,其在癌细胞中的激活会导致上皮-间质转化(EMT)、侵袭、存活、增殖和治疗抗性。癌细胞和各种基质细胞中AXL的激活还会导致肿瘤微环境失调,进而导致血管生成、纤维化、免疫反应和缺氧的调节。更好地理解AXL在这些过程中的作用可能会带来新的治疗方法,使转移性疾病患者受益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/8833413/d79d1c697fce/cancers-14-00466-g001.jpg

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