Naslov
Toll-like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK and HIF

Autori
Matijević Glavan, Tanja ; Cipak Gasparović, Ana ; Vérillaud, Benjamin ; Busson, Pierre ; Pavelić, Jasminka

Izvornik
Molecular carcinogenesis (0899-1987) 56 (2017), 4; 1214-1226

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Toll-like receptor 3 ; cell migration ; metabolism ; poly(A:U) ; poly(I:C)

Sažetak
Toll-like receptor 3 (TLR3) has a dual role in cancer ; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS) and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2) and CD44 variants, which were over-expressed after TLR3 stimulation. TLR3 activation also induced up-regulation of different genes involved in cancer progression (VEGF, MMP9, uPAR) and enzymes involved in glycolytic pathway. Most of the observed effects were Myc- dependent, however, some of them were also connected with MAPK and HIF signaling pathways. Since TLR3 agonists are being investigated as potential novel cancer therapy adjuvants and apoptosis inducers, alone or in combination with other therapeutic options, data presented here suggest extreme caution before their introduction into clinical practice. The fact that TLR3 ligands (poly(I:C) and poly(A:U)) can also aid cancer survival and progression, through induction of metabolic reprogramming, emphasizes the need to investigate this particular topic. Our data suggest that the combination of TLR3 ligands with Myc or MAPK inhibitors may be a way to neutralize their undesirable effects while enhancing their anti-tumor effect.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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