PAK1-dependent MAPK pathway activation is required for colorectal cancer cell proliferation

• DOI: 10.1007/s13277-012-0327-1
• Publication Date: 2012-01-17T10:59:24Z
• Authors: Haitao Qing; Wei Gong; Yufang Che; Xinying Wang; Liang Peng; Yan Liang; Weifei Wang; Qiliang Deng; Hongquan Zhang; Bo Jiang
• Keywords: Tensin; PAK1; CDC42; Securin

P21-activated protein kinase1 (PAK1), a main downstream effector of small Rho GTPases, Rac1, and Cdc42, plays an important role in the regulation cell morphogenesis, motility, mitosis, angiogenesis. Despite its importance, molecular mechanisms PAK1 that contributed to colorectal carcinogenesis remain unclear. Our immunohistochemistry showed expression was increased with cancer (CRC) progression through adenoma carcinoma sequence. Furthermore, our results suggested relationship between nuclear localization Dukes staging. In present study, we knockdown decreased proliferation delayed G1/S cell-cycle transition, apoptosis vivo vitro. addition, knock-down downregulated c-Jun amino terminal kinases (JNK) activity levels cyclinD1, CDK4/6. Inhibition JNK by chemical inhibitor (SP600125) significantly reduced effects on CRC via accumulation phosphatase tensin homolog deleted chromosome 10 (PTEN). conclusion, demonstrate could enhance chemosensitivity CRCs 5-fluorouracil G1 arrest. The mechanism which induced growth might involve activation as well downregulation PTEN. Targeting may represent novel treatment strategy for developing chemotherapeutic agents.