Abstract
The cancer stem cell (CSC) concept suggests that neoplastic clones are maintained exclusively by a rare group of cells possessed with stem cell properties. CSCs are characterized by features that include self-renewal, pluripotency and tumorigenicity, and are thought to be solely responsible for tumor recurrence and metastasis. A hierarchically organized CSC model is becoming increasingly evident for various types of cancer, including prostate cancer. The CD44 (+), CD133 (+) cell subpopulations were isolated from human prostate tumors which exhibit stem-like properties showing therapeutic-resistance, capacity of self-renewal, and exact recapitulation of the original tumor in vivo. Thus, an important challenge is to find measures to eliminate these cancer stem cells, which will stop tumor growth and prevent disease-recurrence. However, knowledge about molecular features critical for the survival of prostate cancer stem cells (PCSC) is meager. Here we report that inhibition of 5-lipoxygenase (5-Lox) by shRNA or MK591 dramatically kills PCSC by inducing apoptosis, suggesting that 5-Lox plays an essential role in the survival of PCSC. Interestingly, MK591 treatment decreases protein levels and inhibits transcriptional activities of Nanog and c-Myc. Since Nanog and c-Myc play important roles as stemness factors, our findings indicate that the 5-Lox activity plays a causal role in maintaining prostate cancer stemness via regulation of Nanog and c-Myc, and suggest that further exploration of 5-Lox-mediated signaling in PCSC may lead to development of novel, target-based, durable strategies to effectively block development and growth of prostate tumors, and prevent prostate cancer recurrence.
Highlights
The concept of cancer stem cell propounds that a small fraction of cells in tumors are capable of selfrenewal and to differentiate into various types of tumor cells, and are responsible for tumor formation, growth, progression and recurrence, while the majority of cells that make up bulk of the tumors are non-tumorigenic end cells [1,2,3]
Since Nanog and c-Myc play important roles as stemness factors, our findings indicate that the 5-Lox activity plays a causal role in maintaining prostate cancer stemness via regulation of Nanog and c-Myc, and suggest that further exploration of 5-Lox-mediated signaling in prostate cancer stem cells (PCSC) may lead to development of novel, target-based, durable strategies to effectively block development and growth of prostate tumors, and prevent prostate cancer recurrence
These findings indicate that 5-Lox activity plays an important role in the survival of PCSC, and suggest that an effective, long-term curative therapy of prostate cancer is possible by targeting 5-Lox with suitable agents to eliminate PCSC via induction of apoptosis
Summary
The concept of cancer stem cell propounds that a small fraction of cells in tumors are capable of selfrenewal and to differentiate into various types of tumor cells, and are responsible for tumor formation, growth, progression and recurrence, while the majority of cells that make up bulk of the tumors are non-tumorigenic end cells [1,2,3]. Cancer stem cells can be extracted from a tumor based on molecular markers, and transplanted to form new tumors, from which the same tumor-propagating cells can again be isolated and re-transplanted [8]. This view puts forth the hypothesis that the vast majority of cells in a tumor undergo differentiation after originating from cancer stem cell and lose their self-renewal potential, and cannot contribute to tumor formation and perpetuation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
