Functional role of Kv1.1 and Kv1.3 channels in the neoplastic progression steps of three cancer cell lines, elucidated by scorpion peptides

Dorra Aissaoui (1, 2, 3) , Saoussen Mlayah-Bellalouna (1, 3) , Jed Jebali (1, 3) , Zaineb Abdelkafi-Koubaa (1, 3) , Soumaya Souid (4, 3) , Wassim Moslah (1, 3) , Houcemeddine Othman (3, 1) , José Luis (5) , Mohamed Elayeb (1, 3) , Naziha Marrakchi (1, 3) , Khadija B Essafi-Benkhadir (4, 3) , Najet Srairi-Abid (3, 1)

1 LR11IPT08 - Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules
2 INSAT Carthage - Institut National des Sciences Appliquées et de Technologie - Carthage
3 UTM - Université de Tunis El Manar
4 LR11IPT04 - Laboratoire d'Epidémiologie Moléculaire et de Pathologie Expérimentale Appliquée aux Maladies Infectieuses
5 INP - Institut de neurophysiopathologie

Voltage-gated potassium (Kv) channels are known to play a pivotal role in the progression of various cancer types and considered as new targets for designing anti-cancer therapy. However, the fact that many Kv channels are expressed in different cell lines makes it difficult to ascribe a functional role for a given Kv channel on a specific aspect of the tumorogenesis. In this work, we showed that although both Kv1.1 and Kv1.3 channels are expressed in U87 (glioblastoma), MDA-MB-231 (breast cancer) and LS174 (colon adenocarcinoma) cells, these respond differently to KAaH1 or KAaH2, two homologous Kv1 blockers from scorpion venom. KAaH1 is active on Kv1.1 and Kv1.3 and was found to inhibit migration and adhesion of U87 cells whereas KAaH2 which is slightly active only on Kv1.1 channel, inhibits their proliferation via the EGFR signaling pathway. The correlation between the electro-physiological activity of the scorpion peptides and their anti-migratory effects suggests the involvement of the Kv1.1 and Kv1.3 channels in the mobility of the three cancer cell lines. Our results showed that besides they can elucidate the implication of Kv1.1 and Kv1.3 channels in molecular mechanisms of neoplastic progression, KAaH1 and KAaH2 may be used as therapeutic tools against glioblastoma.

Mots clés: Adhesion and migration; Cancer; Potassium channel subtypes; Proliferation; Scorpion peptide

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire; Biologie cellulaire; Cancer

Dorra Aissaoui, Saoussen Mlayah-Bellalouna, Jed Jebali, Zaineb Abdelkafi-Koubaa, Soumaya Souid, et al.. Functional role of Kv1.1 and Kv1.3 channels in the neoplastic progression steps of three cancer cell lines, elucidated by scorpion peptides. International Journal of Biological Macromolecules, 2018, 111, pp.1146 - 1155. ⟨10.1016/j.ijbiomac.2018.01.144⟩. ⟨hal-01765752⟩