My research interests and expertise have been directed to the fields of growth factor signaling, steroid receptor/coactivator signaling, and the interplay between these two signaling pathways in cancer progression and metastasis. Our current research interests/projects include:
ERK3 signaling in cancer progression and metastasis. ERK3 is a member of the atypical MAP kinase subfamily. In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning the molecular regulation of ERK3 signaling and its function in cancers. We recently identified a novel function of ERK3 in promoting lung cancer cell invasiveness by phosphorylating SRC-3 (steroid receptor coactivator 3) and regulating its proinvasive activity. In addition, we have found that ERK3 expression is upregulated in multiple cancers, including lung cancer and breast cancer, and its upregulation is associated with cancer invasiveness. These findings suggest that ERK3 may play important roles in cancer progression and metastasis. We are currently pursuing the following projects to elucidate ERK3 signaling cascade and its functions in cancer:
a. To dissect ERK3 signaling pathway utilizing a variety of biochemical approaches including Mass spectrometry-based proteomics: the upstream stimuli and activators and the downstream effectors (substrates).
b. To determine the role of ERK3 signaling in cancer progression and metastasis (currently with a focus on lung cancer) utilizing genetically engineered mouse tumor models with tissue-specific ERK3 knock-in or knock-out.
c. To determine the interplay of ERK3 and SRC-3 in anti-hormone resistance of breast cancer.
Role of SRC-3∆4 in anti-hormone resistant breast and prostate cancer progression and metastasis. Cross-talk between protein kinase signaling and hormone receptor signaling confers anti-hormone resistance and tumor invasiveness in breast and prostate cancers. Interestingly, we have recently found that SRC-3∆4, a splice isoform of SRC-3, not only functions as a transcriptional coactivator of steroid receptors, but also acts as a signaling adaptor to meditate EGF signal transduction and cell motility. These findings suggest that SRC-3∆4 may mediate the cross-talk between growth factor signaling and steroid receptor signaling to promote anti-hormone resistance and tumor invasiveness in breast and/or prostate cancer. To test this hypothesis, the following two projects are being pursued.
a. To define the role of SRC-3Δ4 in the crosstalk between EGF signaling and AR signaling in castration-resistant prostate cancer progression.
b. To investigate whether SRC-3∆4 integrates E2 non-genomic and genomic actions to promote breast cancer progression and elicit anti-estrogen resistance.
