Decoupling tumor cell metastasis from growth by cellular pilot protein TNFAIP8
| Autor: | Li Zhang, Xinyuan Li, Mingyue Li, Youhai H. Chen, Jason R. Goldsmith, Zienab Etwebi, Jiyeon Yu, Songlin Shi, Mayassa J. Bou-Dargham, Lin Wan, Honghong Sun, Ting Li, Ali Zamani |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Lung Neoplasms Skin Neoplasms Fibrosarcoma Biology Article Metastasis Cell membrane Mice Phosphatidylinositol 3-Kinases Cell Movement Cell Line Tumor Genetics medicine Animals Humans Diethylnitrosamine Hippo Signaling Pathway Molecular Biology Cell Proliferation Hippo signaling pathway Cancer Chemotaxis medicine.disease Gene Expression Regulation Neoplastic medicine.anatomical_structure Second messenger system Cancer cell Cancer research Female Tumor necrosis factor alpha Apoptosis Regulatory Proteins Methylcholanthrene |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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