Poster abstracts

Poster number 88 submitted by Rawan Makkawi

Regulation of AKT signaling dynamics by the IGF-IGFBP axis in the lung metastatic microenvironment

Rawan Makkawi (Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University), Vaibhav Murthy (Department of Veterinary Biosciences, The Ohio State University), Alexander Davies (Department of Veterinary Biosciences, The Ohio State University)

Abstract:
The lung is a common metastasis site for various cancers, such as triple negative breast cancer. During metastasis, disseminated cancer cells are able to adapt to the signaling cues in the lung microenvironment, resulting in changes in their signaling pathways and their responsiveness to chemotherapeutics. Of particular interest is the PI3K/AKT pathway, which regulates cell growth and proliferation. It is dysregulated in a variety of human cancers, making it a potential target for therapy. AKT signaling is highly sensitive to Insulin-like growth factor (IGF) and its cognate receptor, IGFR. One of the key regulators of IGF signaling are IGF-binding proteins (IGFBP), a family of proteins that interact with IGF and both positively and negatively modulate its function. Although the IGF-IGFBP signaling has been implicated in several cancers, how IGFBP production by cancer cells and cells of the microenvironment influence cancer cell signaling is yet to be studied in fine detail. We hypothesize that AKT signaling is regulated by the IGF-IGFBP axis in a manner that favors persistent activation of pro-oncogenic AKT signaling in cancer cells. Consistent with this hypothesis, our preliminary data show that changes in IGF levels, or drug treatments, initially suppress AKT signaling but is followed by restoration of AKT signaling in cancer cells to basal levels over time. These changes correlate with altered IGFBP expression profiles in cells of the lung microenvironment, suggesting an adaptive regulatory mechanism to compensate for low AKT signaling. Our future work aims to understand the regulation of cancer cell signaling more fully through IGF and IGFBPs in the metastatic microenvironment and develop strategies to suppress it.

Keywords: Metastatic Microenvironment, AKT Signaling