Epithelial-mesenchymal transition (EMT), a critical process of cancer invasion and metastasis, is associated with stemness property of cancer cells. Though Oct4 and Nanog are homebox transcription factors essential to the self-renewal of stem cells and are expressed in several cancers, the role of Oct4/Nanog signaling in tumorigenesis is still elusive. Here microarray and quantitative real-time PCR analysis showed a parallel, elevated expression of Oct4 and Nanog in lung adenocarcinoma (LAC). Ectopic expressions of Oct4 and Nanog in LACs increased the percentage of CD133-expressing subpopulation and sphere formation, enhanced drug resistance, and promoted EMT. Ectopic expressions of Oct4 and Nanog activated Slug and enhanced the tumorinitiating capability of LAC. Furthermore, double knockdown of Oct4 and Nanog suppressed the expression of Slug, reversed the EMT process, blocked the tumorigenic and metastatic ability, and greatly improved the mean survival time of transplanted immunocompromised mice. The immunohistochemical analysis demonstrated that expressions of Oct4, Nanog, and Slug were present in high-grade LAC, and triple positivity of Oct4/Nanog/ Slug indicated a worse prognostic value of LAC patients. Our results support the notion that the Oct4/Nanog signaling controls epithelial-mesenchymal transdifferentiation, regulates tumor-initiating ability, and promotes metastasis of LAC. Cancer Res; 70(24); 10433-44. Ó2010 AACR.
Hirayama disease (juvenile muscular atrophy of distal upper extremity) is a cervical myelopathy. Predominantly affecting male adolescents, it is characterized by progressive muscular weakness and atrophy of distal upper limbs, followed by spontaneous arrest within several years. Although the cause of cervical myelopathy remains unclear, neuropathologic and neuroradiologic findings suggest a forward displacement of the posterior cervical dural sac during neck flexion, causing compression of the cervical cord, and results in atrophic and ischemic changes in the anterior horn. A good understanding of Hirayama disease is essential because early recognition and management can effectively halt the progressive deterioration.
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