The regulatory heterogeneity in human breast cancer
Cell-to-cell heterogeneity is intrinsic to human cancers. The heterogeneity provides a set of molecular states allowing for flexible cell fate decisions within cancer cell population. Though cancer cell plasticity is widely appreciated, its roles in tumor progression are often unclear.
We have previously developed global approaches that can identify the molecular states of single cells (Nature Methods 7:311-317 [2010]). Our recent work uncovered the natural regulation of receptor-transcription factor circuit in extracellular matrix (ECM)-attached cells (Nature Cell Biology 16:345-56 [2014]), and identified a novel tumor suppressor in triple-negative breast cancer (Developmental Cell 43:418-35 [2017]). We are currently working to understand the mechanism of the cancer cell survival in ECM-poor regions and examine the importance of the regulatory states we identified in 3D organotypic cultures and in breast carcinoma.
Quantitatively understanding the regulation of cancer cell signaling
A striking feature of cancer cells is their ability to reversibly change phenotype: cells detach from ECM, survive in adverse environments and regain their proliferative potential when the ECM has been reestablished. In our lab, we focus on quantitatively understanding the network rewiring that takes place when cancer cells are challenged by diverse microenvironments. We quantitatively measure dynamic changes in the level of biological components to acquire highly adaptable states (Mol Syst Biol 5:246 [2009], J Biol Chem 285:36736-44 [2010]). To better understand the signaling rewiring, we perturb the existing network by using genetic and pharmacological manipulation. Our objective is to systematically define the cellular states and signaling signatures associated with ECM adaptations.