TY - JOUR
T1 - MYADM Activates RhoA-Mediated Amoeboid Migration to Drive Metastasis
AU - Tsai, Yi-Ta
AU - Liu, En-Ting
AU - Yang, Ming-Hsin
AU - Kao, Chien Chang
AU - Tzeng, Sheue-Fen
AU - Chen, Yu-Chi
AU - Hsiao, Pei-Wen
AU - Feng, An-Chieh
AU - Shieh, Grace S
AU - Tsai, Mong-Hsun
AU - Chen, Shau-Kwaun
AU - Chiu, Yi-Lin
AU - Chen, Chin Li
AU - Wu, Sheng-Tang
AU - Meng, En
AU - Tsai, Wen-Chiuan
AU - Chao, Tai-Kuang
AU - Sun, Guang-Huan
AU - Chang, Sun-Yran
AU - Hung, Mien-Chie
AU - Cha, Tai-Lung
PY - 2025/8/29
Y1 - 2025/8/29
N2 - 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.
AB - 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.
U2 - 10.1158/0008-5472.CAN-25-0006
DO - 10.1158/0008-5472.CAN-25-0006
M3 - Article
C2 - 40882023
SN - 0008-5472
JO - Cancer Research
JF - Cancer Research
ER -
