Using a validated tetracycline‐off‐inducible CD44 expression system in mouse model, we have previously demonstrated that the hyaluronan (HA) receptor CD44 promotes breast cancer (BC) metastasis to the liver. To unravel the mechanisms that underpin CD44‐promoted BC cell invasion, RNA samples were isolated from two cell models: (a) a tetracycline (Tet)‐Off‐regulated expression system of the CD44s in MCF‐7 cells and; (b) as a complementary approach, the highly metastatic BC cells, MDA‐MB‐231, were cultured in the presence and absence of 50 µg/mL of HA. Kynureninase (KYNU), identified by Microarray analysis, was up‐regulated by 3‐fold upon induction and activation of CD44 by HA; this finding suggests that KYNU is a potential novel transcriptional target of CD44‐downtstream signalling. KYNU is a pyridoxal phosphate (PLP) dependent enzyme involved in the biosynthesis of NAD cofactors from tryptophan that has been associated with the onset and development of BC. This review will attempt to identify and discuss the findings supporting this hypothesis and the mechanisms linking KYNU cell invasion via CD44.

Neurodegenerative disorders include neurological conditions that affect nerve cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination, and mental functioning. The molecular mechanisms underpinning neurodegenerative disease pathogenesis are still unclear. Nonetheless, several experimental pieces of evidence demonstrate that the perturbation of mitochondrial function and dynamics plays an essential role. In this context, mitochondrial biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number, plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell division and variations in energy demand in response to extracellular stimuli; therefore, it may represent a promising therapeutic target for developing new curative approaches to prevent or counteract neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have already been proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various tissues, including the nervous tissue, and an ever-growing number of studies highlight its neuro-therapeutic potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT, TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in the context of neurodegenerative diseases.

Our tetracycline-off-inducible CD44 expression system previously established in mouse model, revealed that activation of CD44 with its major ligand hyaluronan (HA) promoted breast cancer (BC) metastasis to the liver. To identify the mechanisms that underpin CD44-promoted BC cell invasion, microarray gene expression profiling using RNA samples from (Tet)-Off-regulated expression system of CD44s in MCF7 cells, revealed a set of upregulated genes including, nuclear sirtuin-1 (SIRT1 also known as NAD-dependent deacetylase), an enzyme that requires NAD+ as a cofactor to deacetylate several histones and transcription factors. It stimulates various oncogenic pathways promoting tumorigenesis. This data suggests that SIRT1 is a potential novel transcriptional target of CD44-downstream signaling that promote BC cell invasion/metastasis. This review will discuss the evidence supporting this hypothesis as well as the mechanisms linking SIRT1 to cell proliferation and invasion.

Breast Cancer (BC) is the most common and the major health issue in women worldwide. Metastasis, a multistep process, is the worst aspect of cancer and tumor cell invasion is the defining step. Tumor cell invasion requires cell adhesion molecules (CAMs), and alterations in CAMs is considered as an initiating event in metastasis. Among CAMs, CD44 is a large family of more than 100 isoform, and its precise function was initially controversial in BC. Therefore, we have previously established a (Tet)-off inducible expression system of CD44 in MCF-7 primary BC cell line, and showed that CD44 promoted BC invasion/metastasis both in vitro and in vivo. A microarray gene expression profiling revealed more than 200 CD44-downstream potential transcriptional target genes, mediating its role in BC cell invasion and metastasis. Among these CD44-target genes, the Pre-mRNA cleavage complex 2 protein (PCF11) was upregulated upon the activation of CD44 by its major ligand hyaluronan (HA); This prompted us to hypothesize PCF11 as a potential novel transcriptional target of CD44-promoted BC cell invasion and metastasis. A large body of evidence from the literature supports our hypothesis that CD44 might regulate PCF11 via MAPK/ERK pathway. This review aims to discuss these findings from the literature that support our hypothesis, and further provide possible mechanisms linking CD44-promoted cell invasion through regulation of its potential target PCF11.

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