PKC-Beta signatures in the Tumor Microenvironment
Herzog, Julius
Herzog, Julius
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Abstract
Malignant tumors are complex tissues composed of a network of many different cell types that support the growth and survival of the cancer. Studying the cellular and molecular composition of stromal cells in the tumor microenvironment (TME) may provide an opportunity to identify disease mechanisms and therapeutic targets. The enzyme protein kinase C-β (PKC-β) has emerged as an important signaling mechanism in stromal cells that is required to support cancer cell survival and drug resistance. Although stromal cell PKC-β is required for cancer cell growth, the role of this signaling pathway in the TME remains poorly understood. By analyzing RNA-sequencing transcriptomic data from tumor-adjacent (stromal) co-culture models with chronic lymphocytic leukemia (CLL) cells, our preliminary analysis in the Frietzelab has established a distinct stromal cell PKC-β gene signature, including 625 distinctive genes, the expression patterns of which are associated with resistance to chemotherapy in CLL. This research tests the hypothesis that the PKC-β signature is enriched in distinctive subtypes of cancer associated fibroblasts. We analyze primary and publicly available single cell RNA-seq datasets to identify the PKC-β gene signature to then study specific populations of cancer associated fibroblasts (CAFs) that express PKC-β gene signatures. In the future we plan to investigate the PKC-β pathway in the context of tumor tissues by re-analyzing available spatial transcriptomics data.
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Undergraduate
Date
2024-01-01