It has been demonstrated that cancer cells can instruct cancer associated host cells (CAFs) to provide fuels and building blocks for the rapid growth of cancer cells by reprogramming the energy metabolism of CAFs. The change in cell metabolism leads to lactate accumulation and acidification in the tumor microenvironment, both of which can compromise the effectiveness of cancer treatment. However, the lack of experimental methods that allow researchers to selectively manipulate the metabolic activity and flux of metabolites between cancer cells and CAFs in real-time manner has prevented dissecting the molecular mechanisms underlying metabolic synergy and made it difficult to evaluate the cont...

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It has been demonstrated that cancer cells can instruct cancer associated host cells (CAFs) to provide fuels and building blocks for the rapid growth of cancer cells by reprogramming the energy metabolism of CAFs. The change in cell metabolism leads to lactate accumulation and acidification in the tumor microenvironment, both of which can compromise the effectiveness of cancer treatment. However, the lack of experimental methods that allow researchers to selectively manipulate the metabolic activity and flux of metabolites between cancer cells and CAFs in real-time manner has prevented dissecting the molecular mechanisms underlying metabolic synergy and made it difficult to evaluate the contribution of metabolic synergy in tumor growth. We recently discovered that aberrant fibroblast growth factor (FGF) signaling regulates cell energy metabolism via activating type 1 FGF receptor (FGFR1), demonstrating that the FGF signaling axis is a model suitable for dissecting the contribution of cancer cells and CAFs in this metabolic synergy. Therefore, in this application, we propose to develop and use light-controlled FGFR1 to precisely manipulate the amplitude and duration of FGFR1 signaling in both cancer cells and CAFs in a time- and cell type-specific manner. This cutting-edge research technology permits the real-time study on how cancer cells reprogram the energy metabolism of CAFs and how changes in cell energy metabolism contributes to cancer growth, progression, and metastasis. Findings from this project will yield novel insights into how cancer cells override the intrinsic metabolism control of CAFs. The potential impact of the proposed studies is very high because the knowledge gained through the use of these new research technologies will not only yield novel insights into the role of metabolism in tumor growth, but also provide new opportunities for the development of novel anti-cancer therapies.

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