Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets

Abstract

Aberrant metabolism is a major hallmark of cancer. Abnormal cancer metabolism, such as aerobic glycolysis and increased anabolic pathways, has important roles in tumorigenesis, metastasis, drug resistance, and cancer stem cells. Well-known oncogenic signaling pathways, such as phosphoinositide 3-kinase (PI3K)/AKT, Myc, and Hippo pathway, mediate metabolic gene expression and increase metabolic enzyme activities. Vice versa, deregulated metabolic pathways contribute to defects in cellular signal transduction pathways, which in turn provide energy, building blocks, and redox potentials for unrestrained cancer cell proliferation. Studies and clinical trials are being performed that focus on the inhibition of metabolic enzymes by small molecules or dietary interventions (e.g., fasting, calorie restriction, and intermittent fasting). Similar to genetic heterogeneity, the metabolic phenotypes of cancers are highly heterogeneous. This heterogeneity results from diverse cues in the tumor microenvironment and genetic mutations. Hence, overcoming metabolic plasticity is an important goal of modern cancer therapeutics. This review highlights recent findings on the metabolic phenotypes of cancer and elucidates the interactions between signal transduction pathways and metabolic pathways. We also provide novel rationales for designing the next-generation cancer metabolism drugs.

Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell Renal Cell Carcinoma

“…Actually, PI3K-Akt signaling has been commonly known to regulate insulin-based glucose metabolism and mutations of the pathway genes resulting in aberrant signaling activation, thus leading to higher amount of glucose uptake [ 46 ]. And activation of PI3K-Akt signaling provokes the expression of HIF-1α, which is a transcription factor generally known be involved in the cellular adaption to hypoxia and modulates cellular anaerobic metabolism [ 47 ].…”

Circ_0000003 regulates glutamine metabolism and tumor progression of tongue squamous cell carcinoma via the miR‑330‑3p/GLS axis

“…In the current research, we verified that miR-330-3p directly bound to GLS 3'-UTR and negatively regulated GLS expression. Aberrant energy metabolism, such as increased glutamine catabolism, is one of critical hallmarks of cancer (33,34). In addition to abnormal glycolysis, several previous studies revealed that enhanced glutamine metabolism was correlated with tumor metastasis and poor prognosis in patients with cancer (12,35).…”

Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells

“…According to the original version of the “Warburg hypothesis”, cancer cells switch to glycolysis from oxidative phosphorylation. However, more recent data indicate that many cancer cells, while upregulating glycolysis (as well as glutaminolysis, and many additional metabolic pathways) can also maintain or even increase their aerobic ATP generation via the stimulation of mitochondrial electron transport [ 101 , 102 , 103 , 104 , 105 , 106 ]. To anthropomorphize: maximizing ATP generation is the cancer cell’s primary “metabolic goal”: whatever biochemical mechanism serves this goal—even if it is ”wasteful” or perhaps useful in the short-term but detrimental in the longer-term—will be deemed ‘good enough’ to satisfy the “short-term thinking” of the cancer cell.…”