Ko Yeo Gyeong, Jo Jung Hyun, Song Si Young, Lee Hee Seung
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
FASEB J. 2025 Jan 15;39(1):e70284. doi: 10.1096/fj.202402522R.
Cancer metastasis is the leading cause of cancer-related deaths, making early detection and the prevention of metastatic progression critical research priorities. Recent studies have expanded our understanding of CEMIP (KIAA1199, HYBID), revealing its involvement in cancer metastasis and its potential role in slowing cancer progression. CEMIP plays critical roles in several stages of cancer metastasis: First, CEMIP promotes cancer cell proliferation to maintain cell heterogeneity before the metastasis process. Second, it facilitates cancer cell detachment by promoting the epithelial-mesenchymal transition (EMT) through alterations in signaling pathways. Third, CEMIP contributes to cancer cell adherence and attachment by enabling cells to withstand cell death (anoikis and ferroptosis) and hypoxia. Fourth, during the invasion process, CEMIP induces hyaluronan depolymerization and further modulates signaling to promote EMT. Lastly, in the pre-metastatic niche, CEMIP influences the tumor microenvironment through hypoxia, angiogenesis, signaling pathway changes, and hyaluronan degradation. Recent studies have focused on leveraging CEMIP as a diagnostic tool or a predictor of metastasis and/or targeting CEMIP to overcome cancer resistance and progression. This review aims to explore the role of CEMIP at each stage of cancer metastasis and highlight recent advances in targeting CEMIP to inhibit cancer progression.
癌症转移是癌症相关死亡的主要原因，因此早期检测和预防转移进展成为关键的研究重点。最近的研究扩展了我们对CEMIP（KIAA1199，HYBID）的理解，揭示了它在癌症转移中的作用及其在减缓癌症进展中的潜在作用。CEMIP在癌症转移的几个阶段发挥着关键作用：首先，CEMIP促进癌细胞增殖，以在转移过程之前维持细胞异质性。其次，它通过改变信号通路促进上皮-间质转化（EMT），从而促进癌细胞脱离。第三，CEMIP通过使细胞能够抵抗细胞死亡（失巢凋亡和铁死亡）和缺氧，促进癌细胞黏附和附着。第四，在侵袭过程中，CEMIP诱导透明质酸解聚，并进一步调节信号以促进EMT。最后，在转移前微环境中，CEMIP通过缺氧、血管生成、信号通路变化和透明质酸降解影响肿瘤微环境。最近的研究集中在利用CEMIP作为诊断工具或转移的预测指标，和/或靶向CEMIP以克服癌症耐药性和进展。本综述旨在探讨CEMIP在癌症转移各阶段的作用，并强调靶向CEMIP抑制癌症进展的最新进展。
