Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer

Abstract

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will (i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as mediators of intracellular signaling pathways (ii) analyze the main metabolic changes occurring in cancer development and the role of oncogenic signaling in supporting aberrant lipid metabolism and (iii) discuss combination strategies as powerful new approaches to cancer treatment. The second part of the review will address the emerging role of CK2, a conserved serine/threonine protein kinase, in lipid homeostasis with an emphasis regarding its function in lipogenesis and adipogenesis. Evidence will be provided that CK2 regulates these processes at multiple levels. This suggests that its pharmacological inhibition combined with dietary restrictions and/or inhibitors of metabolic targets could represent an effective way to undermine the dependency of cancer cells on lipids to interfere with tumor progression.

Cooperative Blockade of CK2 and ATM Kinases Drives Apoptosis in VHL-Deficient Renal Carcinoma Cells through ROS Overproduction

“…The same analysis, using BP terms enriched following treatment with CX-4945 alone, showed the presence of the same two major functional modules (Supplementary Figure S8A). In agreement, CK2 inhibition has already been shown to affect the cell cycle, metabolism and mitochondrial functions [40,[89][90][91]. Furthermore, a comparison of the levels of deregulation of the major biological processes, defined by the Normalized Enriched Score (NES), showed that they were overall more deregulated in the KU-60019/CX-4945 condition than with CX-4945 alone (Supplementary Figure S6E).…”

Contribution of the CK2 Catalytic Isoforms α and α’ to the Glycolytic Phenotype of Tumor Cells

“…The CK2 implication in cancer energetics can be also inferred by its regulatory role on Akt and its effectors mTORC1 and β-catenin [ 17 , 18 ], ultimately affecting the modulation of key metabolic targets, as recently described [ 19 ]. Moreover, CK2 plays a role in adipocyte metabolism [ 20 ], and its possible implication in cancer aberrant lipid metabolism has been hypothesized [ 21 ].…”

Identification of a Lipid Metabolism-Associated Gene Signature Predicting Survival in Breast Cancer

“…[3,4] Increased cancer cell proliferation requires the rapid synthesis of lipids for the generation of biological membranes and lipid provide cancer cells with energy during times of nutrient depletion, lipids are also important signalling molecules. [2,5] The synthesis of lipids in healthy organisms is tightly controlled and responds to the nutrient's status of the cell. However, many human cancers display aberrant lipid metabolism.…”

“…However, many human cancers display aberrant lipid metabolism. [5] Next generation sequencing capabilities are revolutionizing approaches to all elds of medicine,recent advances in our understanding of tumor biology have uncovered a growing list of clinically relevant biomarkers. [6] However, the vast majority of studies have concentrated mainly on a single gene, and its predictive ability is insu cient compared with multiple biomarker-based models.…”