Naslov
Responsiveness to GANT-61 inhibitor of GLI1, GLI2 and GLI3 knock-out ovarian cancer cell lines

Autori
Rinčić, Nikolina ; Sabol, Maja ; Trnski, Diana ; Musani, Vesna ; Ozretić, Petar ; Levanat, Sonja

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

Izvornik
Translating Science of Medicine - Targets and Therapeutics, Fifth Meeting of the Croatian Association for Cancer Research with International Participation : Poster presentations, in Libri oncologici, Vol. 46 No. Supplement 1 / Ozretić, Petar ; Levanat, Sonja - Zagreb : Klinički bolnički centar Sestre milosrdnice, 2018, 81-81

Skup
5th Meeting of the Croatian Association for Cancer Research with International Participation: Translating Science to Medicine "Targets and Therapeutics" (HDIR-5)

Mjesto i datum
Zagreb, Hrvatska, 08.11.2018. - 10.11.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Hedgehog signaling ; ovarian cancer ; CRISPR-Cas9 ; GANT

Sažetak
Hedgehog signaling pathway is a developmental signaling pathway which is dormant in most adult differentiated tissues, but aberrantly activated in various tumors. In ovarian tumors it can be activated in a canonical way, by the SHH ligand, or the non-canonical way, by upregulation of the GLI transcription factors. Usually, only GLI1 expression was associated with tumor progression, but GLI2 and GLI3 also play a role by modifying the activity of GLI1 and transcription of their common transcriptional targets. In ovarian cancer, GLI3 protein is expressed in the full-length activator form, and not the shortened repressor form which is the predominant form for GLI3 protein. To study the roles of the three GLI proteins in detail, we used the CRISPR/Cas9 guided gene editing to generate knock-out lines for each of the three GLI proteins. The knock- out was confirmed by Western blot. The modified cell lines showed differences in cell morphology compared to the original SKOV3 cell line immediately after expansion from the single cell, as well as different response to GANT-61 inhibition on cell cycle, apoptosis and colony forming capabilities of the cell lines. This demonstrates that all three GLI proteins are important for survival of ovarian cancer, and not only GLI1 as was considered previously.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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