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    Home > Research & Grants > Grants Program > Research Grants > Research Grants Awarded > Abstract

    Research Grants Awarded

    Dissecting the Mechanism of Cancer Stem Cells in Mammary Tumorigenesis

    Study Section:
    Postdoctoral Fellowship

    Scientific Abstract:
    The identification of cancer stem cells (CSCs) in several types of cancer has led to the hypothesis that cancer is initiated and maintained by a small number of CSCs within a tumor. CSCs have unlimited self-renewal ability, and they generate tumor cell progeny, which represent the bulk of tumor mass but are no longer tumorigenic. This hypothesis has profound implications on how to study and treat cancer. However, it is still unknown how general is the role of CSCs in different types of cancer, and how CSCs self-renew and generate tumors. Answering these questions is urgent for validating the cancer stem cell model and developing therapies that target CSCs. My research will focus on investigating the role of CSCs in breast cancer, and studying the mechanisms of how breast CSCs self-renew and differentiate into non-tumorigenic progeny, as well as how CSCs contribute to tumor metastasis and cancer therapy resistance. For these studies, I plan to develop a novel approach for isolating CSCs based on the slow-cycling property of stem cells, which should allow the identification of CSCs from various types of cancer even with limited knowledge of CSC-specific markers. Combining this approach with current breast cancer stem cell isolation procedures, I plan to enrich CSCs to a high enough purity for subsequent molecular and cellular studies. Transcriptome analysis and other genomic approaches will be performed to identify potential regulators and markers of CSCs, which may allow understanding the molecular mechanisms that control CSC behaviors. These CSC markers can be used to identify CSCs in situ within a tumor, and allow identification of potential CSC niches. In addition, CSC markers can be used to monitor the behaviors of CSCs both during tumor metastasis and in response to cancer therapy. In parallel to the studies on CSCs, I plan to identify and study normal mammary stem cells through similar approaches. Normal stem cells are more homogenous, and are easier to study compared to CSCs. On the other hand, the properties of normal stem cells are often shared by CSCs. Thus, studying normal stem cells may help us better understand cancer stem cells.

    Lay Abstract:
    The cancer stem cell model proposes that tumors are initiated and maintained by a small group of highly tumorigenic (capable of generating tumors) tumor cells, called cancer stem cells (CSCs). Within a tumor, only CSCs have unlimited self-renewal ability. These CSCs then generate tumor cell progeny, which represent the bulk of tumor mass but are no longer tumorigenic. Although current cancer therapies can shrink tumor mass, they fail to effectively target CSCs, which often leads to tumor relapse. Therefore, understanding the exact roles and mechanisms of CSCs in cancer development is critical for developing more effective cancer therapies. Putative CSCs have been identified in several types of cancer, including breast cancer. However, it is still not clear how general is the role of CSCs in different types of cancer, including different subtypes of breast cancer, and what is the mechanism of CSCs in tumorigenesis. My research will focus on investigating the role of CSCs in breast cancer, and studying the mechanisms of how breast CSCs self-renew and differentiate into non-tumorigenic progeny, and how CSCs contribute to tumor metastasis and cancer therapy resistance. For these studies, I plan to develop a novel approach to isolate CSCs based on their infrequent cell division, an intrinsic property of stem cells. Combing this approach with current CSC isolation procedures, I plan to isolate CSCs to high purity for studying the mechanisms that control CSC behaviors. Genomic and additional approaches will be used to study these mechanisms. In parallel to the studies on CSCs, I plan to identify and study normal mammary stem cells through similar approaches. Normal stem cells are more homogenous, and are easier to study compared to CSCs. On the other hand, the properties of normal stem cells are often shared by CSCs. Thus, studying normal stem cells may help us better understand cancer stem cells.