TITLE:
Wnt5a Role in Cisplatin Effect and Selectivity Augmentation in Cancer Therapy
AUTHORS:
Waleed O. Atta, Ahmed Z. Abdel Azeiz
KEYWORDS:
Cisplatin, Malignant Cells, Wnt5a
JOURNAL NAME:
Open Access Library Journal,
Vol.8 No.6,
June
28,
2021
ABSTRACT: Wnt5a is a representative protein ligand that activates a beta catenin independent pathway in Wnt signaling in cancer progression and spread in the palmitoylated form. So that its synthesis is augmented through promotion of its gene transcription in the malignant cells. Cisplatin is an important chemotherapeutic drug used in treatment of different types of advanced cancer. However, its usage is limited due to severe dose-limiting side effects, due to the lack of targeting therapy of cisplatin. On the other hand, the cancer cells developed resistance from cisplatin that is solved partially by C-glycosylation of cisplatin. Through this review article, we strongly suggest that the Wnt5a protein can be used as drug delivery molecule for cisplatin to target the malignant cells. This can be performed through the following steps: Firstly: use of Wnt5a in the depalmitoylated form to avoid its effect on cancer progression with improvement of its binding efficacy by two suggested modifications: 1) Glycosylation with sialic acid-containing glycoside to increase the binding affinity with the sialic acid on the surface of the malignant cells; 2) GPI anchoring modification: This can be performed through the Serine 282 in the Wnt5a molecule. Secondly, binding of the C-glycosylated cisplatin molecule with the modified Wnt5a molecule through the C-glycosylation bond. Since one Wnt5a molecule contains four asparagine molecules, it can bind with four molecules of C-glycosylated cisplatin molecules, hence higher concentration of cisplatin will attack one malignant cell.