Cancer stem cell biology: from leukemia to solid tumors.

Division of Hematology/Oncology, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 703, Rochester, New York 14642, USA.
Current Opinion in Cell Biology (Impact Factor: 8.74). 01/2005; 16(6):708-12. DOI: 10.1016/
Source: PubMed

ABSTRACT The biology of stem cells and their intrinsic properties are now recognized as integral to tumor pathogenesis in several types of cancer. This observation has broad ramifications in the cancer research field and is likely to impact our understanding of the basic mechanisms of tumor formation and the strategies we use to treat cancers. A role for stem cells has been demonstrated for cancers of the hematopoietic system, breast and brain. Going forward it is likely that stem cells will also be implicated in other malignancies. Hence, a detailed understanding of stem cells and how they mediate tumor pathogenesis will be critical in developing more effective cancer therapies.

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    ABSTRACT: The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3β and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3β/CTNNB1 pathway, and may contribute to progression and metastasis of RCC.
    Scientific Reports 03/2015; 5:8997. DOI:10.1038/srep08997 · 5.08 Impact Factor
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    ABSTRACT: Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield long-lasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells (CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, to date, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.

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Aug 6, 2014