Sunitinib Treatment of VHL C162F Cells Slows Down Proliferation and Healing Ability via Downregulation of ZHX2 and Confers a Mesenchymal Phenotype

Stéphanie Buart (1) , M’boyba Khadija Diop (2) , Isabelle Damei (1) , Salem Chouaib (1, 3)

1 INTIM - Immunologie intégrative des tumeurs et immunothérapie des cancers
2 AMMICa - Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse
3 Gulf Medical University [Ajman, UAE]

Mutations of the von Hippel-Lindau (VHL) gene lead to VHL disease in patients. It is characterized by numerous benign and malignant tumors in different organs, as highly vascularized clear cell renal cell carcinomas (ccRCCs). The aim of this study was to examine the consequences of VHL-C162F mutation on morphology, proliferation, ability to form colony and healing ability of renal carcinoma cells. We found that VHL-C162F cells display a higher healing ability than wild type (WT) VHL cells. This was associated with a high expression of ZHX2, an oncogenic driver of ccRCCs. More importantly, sunitinib treatment resulted in a decreased proliferation of VHL-C162F cells. This was associated with ZHX2 inhibition and downregulation of PERK. Such treatment also confers a more mesenchymal profile which is not in favor of survival for patients with VHL-C162F disease.

Mots clés: ccRCCs; VHL-C162F mutation; ZHX2; sunitinib; hypoxia-related genes; epithelial mesenchymal transition

Domaines: Sciences du Vivant [q-bio]

Stéphanie Buart, M’boyba Khadija Diop, Isabelle Damei, Salem Chouaib. Sunitinib Treatment of VHL C162F Cells Slows Down Proliferation and Healing Ability via Downregulation of ZHX2 and Confers a Mesenchymal Phenotype. Cancers, 2023, 16, ⟨10.3390/cancers16010034⟩. ⟨hal-04483601⟩