Abstract 539: Furin predicts prognosis and promotes PTC progression and metastasis via MEK-ERK axis

Abstract

Abstract Furin belongs to the proprotein convertase family and its expression has been documented in various types of cancers, but its role in Thyroid cancer remains unclear. We investigated the expression of Furin in a large cohort of middle eastern PTC patient’s samples and explored its functional role and mechanism in PTC cell line in vitro and in vivo. Furin overexpression was observed in 44.6% of all PTC cases and it was significantly associated with aggressive clinicopathological parameters and poor outcome. We show that inactivation of Furin suppresses tumor growth, proliferation, migration, invasion, spheroid growth and progression of EMT in BRAF mutant cells, whereas its overexpression in BRAF wild-type PTC cell lines reversed the effect. Mechanistically, Furin inactivation caused MEK/ERK pathway suppression in BRAF mutant cells, while inhibition of MEK has no effect on Furin expression which suggest Furin is a functional upstream of MEK/ERK Pathway. Furthermore, study revealed the synergistic antitumor effect of Furin depletion and MEK inhibitor. These results indicate that Furin is an important prognostic marker and its inhibition can be a potential therapeutic target for aggressive PTC. Citation Format: Pratheeshkumar Poyil, Abdul K. Siraj, Divya Padmaja, Sandeep Kumar Parvathareddy, Roxanne Diaz, Saravanan Thangavel, Rafia Begum, Wael Haqawi, Khadija Alobaisi, Falah Hassan Al-Mohanna, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya. Furin predicts prognosis and promotes PTC progression and metastasis via MEK-ERK axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 539.