Cancer stem cells (CSCs) are involved in tumor-initiation, metastasis, drug resistance, and cancer recurrence. CSCs share many similar biological properties as the embryonic stem cells. Identifying CSCs specific biomarker and studying its underlying mechanism would help us to develop diagnostic and therapeutic tools. We previously used hybridoma technique to identify a novel antibody which specifically recognized the cell surface of undifferentiated human embryonic stem cells and CSCs. Further identifying the target protein was called podocalyxin-like protein 1 (PODXL-1). Our recent studies have demonstrated that overexpression of PODXL-1 promotes tumor invasiveness and metastases in breast and head and neck cancers (Int J Oncol 2014). PODXL-1 promoted tumor metastasis was mediated through activating Rac1/Cdc42/cortactin signaling cascade (Carcinogenesis 2014). We further found that expression of PODXL-1 was correlated with epithelial-mesenchymal transition (EMT) and cancer stemness genes expression, and tumorsphere forming capability in human breast cancer cells. Interestingly, we also found that suppression of PODXL-1 down-regulated Hippo-YAP signaling cascade. Hippo-YAP pathway plays an important role normal stem cell and cancer stem cells. Several recent studies raised an emerging issue on the role of Hippo-YAP in tumorigenesis, invasiveness, and cancer stemness. However, the role of PODXL-1 in EMT and cancer stemness, and the regulatory mechanism in between PODXL-1 and Hippo-YAP is still unclear. According to our previous findings and the preliminary data, we will further investigate (1): the role of PODXL-1 in promoting EMT and breast cancer stemness, (2): the regulatory mechanism of Hippo-YAP signaling in PODXL-1-mediated EMT gene expression and cancer stemness, and (3): the association of PODXL-1 and YAP in clinical outcome in breast cancer, and the identification of therapeutic efficacy of anti-PODXL antibody against breast cancer and cancer stem cells. The goal of this research project will verify that PODXL-1 as a potential biomarker and therapeutic target for breast CSCs.
|Effective start/end date||8/1/15 → 7/31/16|
- Epithelial-mesenchymal transition
- cancer stem cell
- breast cancer
- cancer stemness
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