Publication details
Adaptor protein CIN85 modulates drug resistance of human osteosarcoma cells
| Authors | |
|---|---|
| Year of publication | 2024 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Adaptor protein CIN85 is involved in multiple signaling cascades, including EGFR, HGFR, and PI3K, and regulates endocytosis, cell growth, adhesiveness, and motility. Previously, CIN85 was identified as one of the proteins overexpressed in doxorubicin (DOX)-resistant osteosarcoma (OS) cells. This study aimed to investigate the impact of CIN85 on the survival and drug resistance of OS cells. Parental HOS and SAOS-2 cell lines and DOX-resistant derivatives with CIN85 knockdown or overexpression were used. Cell survival under treatment with DOX or CDDP (cisplatin) was evaluated by MTT assay and Sytox green exclusion assay. PARP content was estimated by Western blotting. Gene expression data were obtained from the GSE154540 dataset. Statistical analysis was performed using Student’s t-test or ANOVA. CIN85 silencing in DOX-resistant HOS and SAOS-2 cells resulted in an increased percentage of Sytox green-positive (dead) cells upon DOX treatment thus leading to the elevated sensitivity to DOX. Parental HOS cells with CIN85 knockdown were characterized by increased sensitivity to DOX, and especially to CDDP treatment. Vice versa, CIN85-overexpressing HOS cells were less sensitive to both DOX and CDDP by 30 %. CIN85-silenced SAOS-2 cells demonstrated elevated sensitivity to both DOX and CDDP by 35 % and 55 %, respectively, and CIN85 overexpression resulted in a reduction of the percentage of Sytox green-positive cells after DOX and CDDP treatments by 30 %. In addition, increased content of cleaved PARP was observed in CIN85-silenced cells. RNA sequencing of cell variants with CIN85 overexpression/knockdown will help to unravel the molecular mechanism of CIN85-dependent chemoresistance. These findings were complemented with the analysis of CIN85 expression in OS samples of patients with good versus poor response to chemotherapy, which found that CIN85 expression is slightly higher in the cohort of poor-responders. Taken together, the obtained results indicate the substantial role of adaptor protein CIN85 in the acquisition of chemoresistance by osteosarcoma cells. |
| Related projects: |