Naslov
First Insights into the Characterization of GANT61 - Resistant Melanoma Cell Lines

Autori
Piteša, Nikolina ; Kurtović, Matea ; Bartoniček, Nenad ; Gkotsi, Danai S, Čonkaš, Josipa ; Petrić, Tina ; Musani, Vesna ; Ozretić, Petar ; Riobo-Del Galdo, Natalia A ; Sabol, Maja

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

Izvornik
Hedgehog signaling: From molecular structure to dveelopmental biology and diseases : Abstract book / - , 2023, 76-76

Skup
Hedgehog signaling: From molecular structure to dveelopmental biology and diseases

Mjesto i datum
Sant Feliu de Guíxols, Španjolska, 24.04.2023. - 27.04.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
HH-GLI ; MAPK ; melanoma ; resistance ; RAB34 ; primary cilia

Sažetak
In melanoma, canonical HH-GLI inhibition proved to be ineffective due to its noncanonical activation through other pathways like RAS/RAF/MAPK. Better understanding of HH-GLI and RAS/RAF/MAPK interactions is critical since these interactions may be crucial in establishment and maintenance of drug resistance. To investigate our hypothesis, we used two approaches, identification of GLI transcriptional targets connected to RAS/RAF/MAPK and establishment of GANT-61 resistant cell lines. We successfully established two GANT-61 resistant melanoma cell lines. First insights revealed that resistant cell lines changed their response to HH-GLI and RAS/RAF/MAPK inhibitors, HH-GLI and RAS/RAF/MAPK signaling activity, invasive properties like migration and colony formation capacity, autophagy efficiency and cell cycle. Our previous study (Kurtović et al. 2022), using a combined ChIP-seq and RNA-seq approach identified RAB34, a novel GLI2 transcription target and potential MAPK substrate. RAB34 essential for ciliogenesis, was downregulated in NRAS mutated resistant cell line which also showed primary cilia loss. We believe that primary cilia represent a potential link between HH-GLI and RAS/RAF/MAPK signaling, therefore, our future studies will focus on ciliogenesis regulation via RAS/RAF/MAPK signaling and its function in drug resistance.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA