Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment

Abstract

While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours. In particular, metabolic alteration in cancer cells are coupled to the modulation of intracellular and extracellular pH, epithelial-to-mesenchymal transition and associated increased invasiveness, autophagy, and the development of anticancer treatment resistance. Finally, based on mechanistic, pre-clinical and clinical studies, we proposed the adjuvant supplementation of dietary n-3 polyunsaturated fatty acids for a complementary holistic treatment of the cancer disease.

Autophagy and mitophagy in cancer metabolic remodelling

“…Through its important contribution in the production of ATP and macromolecules, it is now well described that mitochondria sustain tumour growth and cancer progression. Indeed mitochondrial function has been associated with cancer cell proliferation, resistance to cell death and metastasis (see reviews [8][9][10][11]). Consequently, targeting mitochondria in cancer cells has been proposed to reduce tumour progression [12][13][14].…”

Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…Many other factors of different natures contribute to the pathogenesis, growth and spread of BC through TME acidification, such as hormones like estrogens, insulin, prolactin and sex steroids, growth factors like IGF1, EGF, VEGF and PDGF, as well as ion channels, cytokines and certain interleukins, apart from genetic abnormalities. Most of these factors, if not all, upregulate NHE1 [ 42 , 97 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 ]. Recently, a series of reviews covering the causes and consequences of tumor acidosis in cancer have been made available [ 118 ].…”

Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma

“…It is well known that metabolic networks played key roles in biological regulation, thus controlling the cellular processes in different time scales (Green et al ., ). However, cancer cells fundamentally altered cellular metabolism, which could directly lead to the dysregulation of cell process and eventually change cell fate (Dumas et al ., ; Martinez‐Outschoorn et al ., ). Based on the above observations, circADAMTS13 is likely to regulate HCC metabolism and cellular processes by affecting downstream genes of miR‐484, thereby inhibiting the proliferation of HCC.…”