MYADM Activates RhoA-Mediated Amoeboid Migration to Drive Metastasis

IF 16.6 1区医学 Q1 ONCOLOGY

Cancer research Pub Date : 2025-08-29 DOI:10.1158/0008-5472.can-25-0006

Yi-Ta Tsai, En-Ting Liu, Ming-Hsin Yang, Chien Chang Kao, Sheue-Fen Tzeng, Yu-Chi Chen, Pei-Wen Hsiao, An-Chieh Feng, Grace S. Shieh, Mong-Hsun Tsai, Shau-Kwaun Chen, Yi-Lin Chiu, Chin Li Chen, Sheng-Tang Wu, En Meng, Wen-Chiuan Tsai, Tai-Kuang Chao, Guang-Huan Sun, Sun-Yran Chang, Mien-Chie Hung, Tai-Lung Cha

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引用次数: 0

Abstract

Metastasis, the leading cause of cancer-related mortality, remains the most critical challenge in cancer treatment. Cancer cells can adopt amoeboid migration to facilitate metastasis, highlighting the need elucidate the molecular pathways regulating the amoeboid migration phenotype. Here, we identified that MYADM, a transmembrane protein expressed during myeloid cell maturation, enabled cancer cells to acquire amoeboid migration plasticity, promoting metastasis and contributing to poor patient outcomes. Cancer cells exploited MYADM-mediated adhesion and migration to mimic leukocyte trafficking. By interacting with RhoGDI, MYADM activated RhoA-mediated leukocyte trafficking-associated genes (LTAG) enrichment, invasiveness, membrane blebbing, and anoikis resistance. MYADM modulated chromatin accessibility (CA)-regulatory genes, influencing intermediate filament cytoskeleton dynamics of cancer cells and tumor tissues. MYADM loss in cancer cells triggered CA-driven death signaling, blocking metastasis, which was not observed in monocytes. These findings position MYADM as a potential therapeutic target to disrupt metastasis, offering avenues for clinical intervention.

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MYADM激活rhoa介导的变形虫迁移以驱动转移

转移是癌症相关死亡的主要原因，也是癌症治疗中最关键的挑战。癌细胞可以通过变形虫迁移促进转移，因此需要阐明调节变形虫迁移表型的分子途径。在这里，我们发现MYADM，一种在骨髓细胞成熟过程中表达的跨膜蛋白，使癌细胞获得变形虫迁移可塑性，促进转移并导致患者预后不良。癌细胞利用myadm介导的粘附和迁移来模拟白细胞运输。通过与RhoGDI相互作用，MYADM激活了rhoa介导的白细胞运输相关基因（LTAG）的富集、侵袭性、膜起泡和抗风疹性。MYADM调节染色质可及性（CA）调控基因，影响癌细胞和肿瘤组织的中间丝细胞骨架动力学。癌细胞中MYADM的缺失触发了ca驱动的死亡信号，阻断了转移，而在单核细胞中没有观察到这一点。这些发现将MYADM定位为破坏转移的潜在治疗靶点，为临床干预提供了途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer research 医学-肿瘤学

CiteScore

16.10

自引率

0.90%

发文量

7677

审稿时长

2.5 months

期刊介绍： Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research. With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445. Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.