Oncogenicity of PAKs and Their Substrates

作者: Hong He , Hiroshi Maruta

DOI: 10.1016/B978-0-12-407198-8.00002-3

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摘要: Transformation of normal cells to malignant or benign tumor is caused by mutations in a variety genes that are involved proliferation, apoptosis, angiogenesis, and invasion/metastasis. Oncogenic RAS found more than 30% human cancers (malignant tumors), such as pancreatic colon cancers, activates several signal transducers, kinases (PI-3 kinase RAF) GTPases (RAC CDC42), required for transformation. PAKs Ser/Thr activated RAC CDC42. Mammalian comprise six isoforms (PAK1–6) play important roles actomyosin dynamics, cell survival, proliferation. Among these PAKs, PAK1 PAK4 highly oncogenic activate transducers RAF/MEK/ERK, estrogen receptor, β-catenin, LIM kinase, NFκB, AKT; further, they inactivate few suppressors BAD, FOXO, merlin. Although not mutated either hyperactivated overexpressed 70% particular solid tumors, essential both growth metastasis cancers. Thus, natural synthetic compounds selectively block would have huge therapeutic potential the future. Here, we highlight PAK1/PAK4-dependent tumors effectors (substrates) PAKs.

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