الإنتاج البحثي لأعضاء هيئة التدريس بالكلية V.8 - Flipbook - Page 195
(8) Bragazzi, N. L., & Sellami, M. (2021). Cancer bioenergetics as emerging holistic cancer
theory: the role of metabolic fluxes and transport proteins involved in metabolic pathways in the
pathogenesis of malignancies. State-of-the-art and future prospects. Advances in Protein Chemistry
and Structural Biology, 123, 27–47. https://doi.org/10.1016/bs.apcsb.2020.09.001
Cancer represents a global health concern, imposing a severe burden both from a societal and
clinical perspective. Despite the latest advancements and achievements in the treatment and
management of malignancy, cancer still imposes a dramatically high burden worldwide. Different
theories (biophysical or biochemical, genetic or epigenetic) related to the origin of tumor cells have
been put forth. These theories can also be subdivided into reductionist and emergentist/holistic
theories. In the current overview, we will focus only on the cancer metabolic theory, one of the
emergentist/holistic theories: it is holistic in that maintains that pathways, cascades and networks
controlling energy metabolism, as well as those devoted to cell growth, cell cycle, replication,
division and other cellular processes are highly interwoven and interconnected, and cannot be
understood if not assuming a systems biology perspective. Cells should be seen as metabolic
factories, in which metabolic fluxes and circuits (anabolic and catabolic) are plastically re-wired
on the basis of the internal/external stimuli (cell make-up and genetic determinants, microenvironment, etc.). Complex regulatory and meta-regulatory systems exist that finely tune the
functioning of cell, cell-cell communication and its interaction with the surrounding environment.
At the tissue level, not all tissues share the same degree of metabolic plasticity (metabolic rigidity
vs. metabolic flexibility), even though some metabolic coupling systems exist in order to guarantee
an overall minimum extent of metabolic plasticity. The same broad picture of molecular events is
necessary when describing the impairment and dysregulation of these processes, leading to multistage phenomena, including carcinogenesis.
(9) Sellami, M., & Bragazzi, N. L. (2021). The effect of sport and physical activity on transport
proteins: implications for cancer prevention and control. Advances in Protein Chemistry and
Structural Biology, 123, 17–26. https://doi.org/10.1016/bs.apcsb.2020.07.001
The present contribution briefly overviews the major biological functions of the plasma membrane
and of the transport proteins (transporters), which enable the movement of different molecules and
substrates (either charged or uncharged) by passive (facilitated diffusion) or active transport. In
particular, transporters are overviewed at the level of the skeletal muscles, which represent a highly
complex, heterogeneous, plastic and dynamic tissue and are one of the most abundant tissues in
humans, accounting for up to 40% of their total weight and containing up to 50%–75% of all body
proteins. Moreover, it is shown how sport and physical activity finely tune and modulate human
proteome, especially in terms of structural and functional improvements concerning the density of
the transport proteins. These changes are among the factors responsible for the positive outcomes
of training, which involve mainly the cardiovascular and the endocrine/metabolic systems.
Different kinds of training (strength and endurance) enable to achieve such improvements, even
though there seems to exist a dose-relationship intensity-dependent effect, with responses after 6–
8 weeks of exercise and disappearing in the chronic period (years of training). Finally, exerciseinduced changes at the level of transporters can play a role in terms of cancer prevention and
management. Regular physical activity and exercise can, indeed, counteract the side-effects of
chemotherapy drugs, including doxorubicin and other anthracycline derivatives, which may impair
the functions of cardiac and skeletal muscles, probably modulating the expression of multidrug
resistance proteins.
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