Tumorigenesis in humans is a multi-step process, which reflects various genetic and epigenetic alterations. Tumor invasion and metastasis account for ~90% of all cancer deaths, and the process involves transitions between the epithelial and mesenchymal states (EMT and MET, which also occur during normal organ development). In particular, the EMT process has been implicated in promoting carcinoma invasion and metastasis. Initiation and progression of the EMT programming involves extensive crosstalk between various extracellular and intracellular signaling pathways, as well as regulatory components such as transcription factors (e.g., Twist, Snail1/2, Zeb1/2) and microRNAs (e.g., mir-200). However, the precise mechanisms of EMT are yet to be fully elucidated.
The Hippo signaling pathway is regarded as being critical in the regulation of organ size and tumorigenesis in both mammals and Drosophila. Dysregulation of Hippo pathway components, such as MST1/2, LATS1/2 and YAP, has been observed in human cancers, including hepatocellular carcinoma (HCC), oral squamous cell carcinoma, sarcomas, astrocytomas and breast cancer.
Using molecular, cellular and biochemical approaches as well as the 3-D cell culture system and mouse models, we are intensively investigating the roles of EMT and the Hippo signaling pathway in the initiation and progression of solid carcinomas, e.g., breast cancer.
The ultimate goal of my lab is to unravel the mechanisms of tumor development and metastasis, in the hope of revealing important new diagnostic and prognostic biomarkers, and more importantly, therapeutic strategies for the treatment of human cancer.
- Elucidation of the physiological regulation of the Hippo pathway and its dysregulation in cancer
- Study of mechanisms underlying the EMT in tumorigenesis and metastasis
- Epigenetic regulation of EMT and its cancer stem cell (CSC) properties