Abstract
A hallmark of cancer cells is the ability to rewire their bioenergetics and metabolic signaling circuits to fuel their uncontrolled proliferation and metastasis. Adenylate kinase (AK) is the critical enzyme in the metabolic monitoring of cellular adenine nucleotide homeostasis. It also directs AK→ AMP→ AMPK signaling controlling cell cycle and proliferation, and ATP energy transfer from mitochondria to distribute energy among cellular processes. The significance of AK isoform network in the regulation of a variety of cellular processes, which include cell differentiation and motility, is rapidly growing. Adenylate kinase 2 (AK2) isoform, localized in intermembrane and intra-cristae space, is vital for mitochondria nucleotide exchange and ATP export. AK2 deficiency disrupts cell energetics, causes severe human diseases, and is embryonically lethal in mice, signifying the importance of catalyzed phosphotransfer in cellular energetics. Suppression of AK phosphotransfer and AMP generation in cancer cells and consequently signaling through AMPK could be an important factor in the initiation of cancerous transformation, unleashing uncontrolled cell cycle and growth. Evidence also builds up that shift in AK isoforms is used later by cancer cells for rewiring energy metabolism to support their high proliferation activity and tumor progression. As cell motility is an energy-consuming process, positioning of AK isoforms to increased energy consumption sites could be an essential factor to incline cancer cells to metastases. In this review, we summarize recent advances in studies of the significance of AK isoforms involved in cancer cell metabolism, metabolic signaling, metastatic potential, and a therapeutic target.
Highlights
The significance of metabolism and metabolic signaling in human diseases is rapidly growing
The present review is a snapshot from recent Adenylate kinase (AK) studies that focused on the significance of AK network in energetics and metabolic signaling in cancer cells
Studies indicate that AK isoforms (AK1, Adenylate kinase 2 (AK2), AK4, and AK6) have an important role in the regulation of cancer cell metabolism, metabolic signaling, and cell migration and invasion
Summary
Aleksandr Klepinin 1*, Song Zhang 2, Ljudmila Klepinina 1, Egle Rebane-Klemm 1, Andre Terzic 2, Tuuli Kaambre 1 and Petras Dzeja 2*. Specialty section: This article was submitted to Cancer Metabolism, a section of the journal
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