1. Decoupling tumor cell metastasis from growth by cellular pilot protein TNFAIP8.
- Author
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Li M, Li X, Goldsmith JR, Shi S, Zhang L, Zamani A, Wan L, Sun H, Li T, Yu J, Etwebi Z, Bou-Dargham MJ, and Chen YH
- Subjects
- Animals, Apoptosis Regulatory Proteins genetics, Cell Line, Tumor, Cell Movement, Cell Proliferation, Diethylnitrosamine adverse effects, Female, Fibrosarcoma chemically induced, Fibrosarcoma genetics, Fibrosarcoma metabolism, Gene Expression Regulation, Neoplastic, Hippo Signaling Pathway, Humans, Lung Neoplasms chemically induced, Lung Neoplasms genetics, Lung Neoplasms metabolism, Male, Methylcholanthrene adverse effects, Mice, Phosphatidylinositol 3-Kinases metabolism, Skin Neoplasms chemically induced, Skin Neoplasms genetics, Skin Neoplasms metabolism, Apoptosis Regulatory Proteins metabolism, Fibrosarcoma pathology, Lung Neoplasms pathology, Skin Neoplasms pathology
- Abstract
Cancer metastasis accounts for nearly 90% of all cancer deaths. Metastatic cancer progression requires both cancer cell migration to the site of the metastasis and subsequent proliferation after colonization. However, it has long been recognized that cancer cell migration and proliferation can be uncoupled; but the mechanism underlying this paradox is not well understood. Here we report that TNFAIP8 (tumor necrosis factor-α-induced protein 8), a "professional" transfer protein of phosphoinositide second messengers, promotes cancer cell migration or metastasis but inhibits its proliferation or cancer growth. TNFAIP8-deficient mice developed larger tumors, but TNFAIP8-deficient tumor cells completely lost their ability to migrate toward chemoattractants and were defective in colonizing lung tissues as compared to wild-type counterparts. Mechanistically, TNFAIP8 served as a cellular "pilot" of tumor cell migration by locally amplifying PI3K-AKT and Rac signals on the cell membrane facing chemoattractant; at the same time, TNFAIP8 also acted as a global inhibitor of tumor cell growth and proliferation by regulating Hippo signaling pathway. These findings help explain the migration-proliferation paradox of cancer cells that characterizes many cancers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2021
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