Naslov
Hh-Gli signaling pathway activity in oral squamous cell carcinoma

Autori
Levanat, Sonja ; Sabol, Maja ; Car, Diana ; Ozretić, Petar ; Musani, Vesna ; Leović, Dinko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 36th FEBS Congress / The FEBS Journal 278 (S1) / Perham, Richard - Oxford : Wiley-Blackwell, 2011, 241-241

Skup
The 36th FEBS Congress

Mjesto i datum
Torino, Italija, 25.06.2011. - 30.06.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Hh-Gli signaling ; oral ; oropharyngeal ; squamous cell carcinoma ; SSC

Sažetak
Oral and oropharyngeal squamous cell carcinoma is a relatively common disease but very little is known about the molecular mechanisms responsible for cellular proliferation which include changes in p16INK4A, p53, cyclin D1, FHIT, RASSF1A, EGFR and Rb. The Hedgehog–Gli (Hh-Gli) signaling pathway plays a crucial role in vertebrate embryogenesis, while in adult organism remains active in the regulation of tissue homeostasis, regeneration and stem cell maintenance, but inappropriate activation is implicated in the development of one third of all severe cancers. The categorization of established tumors into abnormal Hh-Gli signaling that initiate tumors or in maintenance the tumor or third not yet defined category might have relevance for prognosis and targeted therapeutics. Activation of the Hh-Gli pathway begins when secreted Hedgehog (Sonic Shh, Indian Idh, or Desert Dh) binds to its receptor Patched, then inhibition of Smoothened, a G-protein coupled receptor by Patched is relieved, and activates downstream intracellular components of the pathway. The transcription of target genes (including Patched and Gli1) is subsequently activated by the Gli family of transcription factors. The role of Hh-Gli signaling pathway in squamous cell carcinoma (SCC) formation has not yet been elucidated. We found expression of main members of Hh-Gli signaling pathway, as well as activation of Survivin expression (inhibitor of apoptosis). Ptch1 was found to be correlated with p16 expression (cell cycle regulator), as well as with Survivin expression. Pathway components were associated with clinical and pathological features. Broders’ grade and N stage were associated with higher Ptch1 and lower Gli1 expression. Tumor stage was negatively associated with Smo expression, and tumor size was positively associated with p16 expression. Ptch1 and Shh were frequently detected in the surrounding stroma. Our results were confirmed in vitro in a corresponding cell line, where it was shown that the pathway is inducible by Shh protein. Our findings contribute to further understanding of the pathway in this type of tumors.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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