NUMERO: #20260259

Título: FROM CHEMORESISTANCE TO TUMORIGENESIS: CISPLATIN REWIRES ORAL CELLS THROUGH THE TGF-B/KAT2B AXIS

Nome do Apresentador: Antônio Secco Martorano

Categoria do Trabalho: Pôster - Investigação Original (IO)

Área Temática: Patologia Oral

Resumo: This study investigated the effects of cisplatin on cellular reprogramming in CAL27 and SCC9 oral carcinoma cells, and in non-tumoral epithelial HaCaT cells. RNA-seq was used to identify changes in gene expression between wild-type (WT) and cisplatin-resistant (CisR) tumor cells. Functional validation included flow cytometry, immunofluorescence, immunohistochemistry, sphere- and colony-formation assays, viability, migration, invasion, cell cycle, and xenograft assays. RT-qPCR and western blotting assessed gene and protein expression. Cisplatin activated pathways related to epithelial-mesenchymal transition (EMT), proliferation, and migration. CisR cells exhibited increased expression of cancer stem cell (CSC) markers, enhanced sphere formation, proliferation, invasion, and xenograft tumor growth. Cisplatin also induced dedifferentiation of non-CSC cells into CSCs, increasing TGF-β and KAT2B expression. Surprisingly, non-tumor HaCaT cells exposed to cisplatin developed a tumor-like phenotype and formed tumors in xenografts. The pharmacological inhibition of TGF-β and KAT2B reduced CSC markers and xenograft tumor volume, indicating their therapeutic potential. In conclusion, cisplatin induced cellular reprogramming and tumorigenesis by EMT activation, CSC accumulation, and TGF-β/KAT2B overexpression. Pharmacological inhibition of the axis reversed CSC accumulation, reduced tumor volume, and increased chemosensitivity, highlighting this as a promising target for antitumor therapies.

Funding: FAPESP 2017/11780-8

Autor 1:  Antônio Secco Martorano

E-mail 1:  [email protected]

Autor 2:   Lucas Dias de Oliveira

E-mail 2:  [email protected]

Autor 3 :  Ana Patrícia Espaladori Eskenazi

E-mail 3:  [email protected]

Autor 4:  Gabriela Camarneiro Siqueira

E-mail 4:  [email protected]

Autor 5:  Raysa Theresa Pinheiro Santos

E-mail 5:  [email protected]

Autor 6:  Luciana Oliveira de Almeida

E-mail 6:  [email protected]