Our primary research interests focus on erbB receptor tyrosine kinases (RTKs)-mediated signal transduction in breast cancer and miRNA-mediated epigenetic regulation of drug resistance and metastasis. By understanding the molecular mechanism of RTK signaling in tumorigenesis and miRNA regulation of tumor progression, we hope to identify novel molecular targets and develop epigenetic approaches with therapeutic potential for cancer treatment.
There are currently three areas of investigation in my laboratory:
Project 1: Role of erbB3 signaling in cancer therapeutic resistance and tumor metastasis. We have reported that activation of the erbB3/PI-3K/Akt signaling plays an important role in the development of resistance to tamoxifen, paclitaxel, and trastuzumab (Herceptin) in erbB2-overexpressing (erbB2+) breast cancer cells. Our recent data show that the erbB3 signaling exerts its biologic function via regulation of two tumor suppressive miRNAs, miR-203 and miR-542-3p. Modern molecular and cellular biological techniques are applied to determine how miR-203 and miR-542-3p contribute to erbB3-mediated therapeutic resistance and tumor metastasis.
Project 2: Identification of novel erbB3-targeted therapy. We have considered the unique biologic features of erbB3 receptor and discovered that the selective class I HDACi entinostat upregulates expression of three erbB3-targeting miRNAs, and induces apoptosis in erbB2+ breast cancer cells via downregulation of erbB3. Our ongoing studies aim to determine whether the novel strategy/agents targeting of erbB3 (cooperative miRNAs and epigenetic modulators) may abrogate or attenuate the therapeutic resistance to tamoxifen, paclitaxel, and/or trastuzumab against erbB2+ breast cancer.
Project 3: Epigenetic enhancement of chemotherapy against non-small cell lung cancer (NSCLC), multiple myeloma (MM), acute myeloid leukemia (AML). We have explored the combinatorial effects of entinostat and chemotherapeutic agents on NSCLC, MM, and AML cells. Our data show that entinostat is able to induce expression of several tumor suppressive miRANs, leading to downregulation of Survivin, and thereby significantly potentiate chemotherapeutics-induced antitumor activity. These studies suggest that miRNA-mediated epigenetic reduction of Survivin (or other anti-apoptosis molecules) is a useful strategy to enhance the efficacy of chemotherapy in cancer treatment.
1. Lee, Y., Ma, J., Lyu, H., Huang, J., Kim, A., and Liu, B. Role of erbB3 receptors in cancer therapeutic resistance. Acta Biochim Biophys Sin 2014, 46: 190–198
2. Ma, J., Lyu, H., Huang, J., and Liu, B. Targeting of erbB3 receptor to overcome resistance in cancer treatment. Molecular Cancer 2014, 13:105 doi:10.1186/1476-4598-13-105
3. Zhu P, Davis M, Blackwelder AJ, Bachman N, Liu B, Edgerton SM, Williams LL, Thor AD, Yang X. Metformin selectively targets tumor-initiating cells in ErbB2-overexpressing breast cancer models. Cancer Prev Res (Phila). 2014; 7(2):199-210. doi: 10.1158/1940-6207. PubMed PMID: 24322659.
4. Huang, J., Lyu, H., Wang, J., and Liu, B. MicroRNA regulation and therapeutic targeting of Survivin in cancer. American Journal of Cancer Research 2015; 5(1):20-31.
5. Huang, J., Lyu, H., Wang, J., and Liu, B. Influence of survivin-targeted therapy on chemosensitivity in the treatment of acute myeloid leukemia. Cancer Letters 2015; 366: 160-172. doi:10.1016/j.canlet.2015.05.033
6. Lyu, H., Huang, J., Edgerton, S.M., Thor, A.D., He, Z., and Liu, B. Increased erbB3 promotes erbB2/neu-driven mammary tumor proliferation and co-targeting of erbB2/erbB3 receptors exhibits potent inhibitory effects on breast cancer cells. International Journal of Clinical and Experimental Pathology 2015; 8(6):6143-6156