Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2

Abstract

Anoctamin 5 (ANO5) is a member of the Anoctamin (ANO) family of calcium-activated chloride channels. Although ANO5 expression is upregulated in various cancers, its role in osteosarcoma remains largely unknown. In this study, bioinformatics analysis, western blot, and immunohistochemical staining revealed that ANO5 was upregulated in osteosarcoma cell lines and osteosarcoma tissues, and ANO5 expression was positively associated with tumor size, tumor grade, and metastasis. Functional experiments demonstrated that inhibition of ANO5 decreased, while ANO5 overexpression increased, osteosarcoma cell proliferation and mobility in vitro . Immunoprecipitation, western blot, and confocal microscopy experiments showed that ANO5 bound to and promoted the degradation of Nel-like proteins 1 (NELL1) and 2 (NELL2). Moreover, a subcutaneous tumor transplantation model revealed that ANO5 knockdown reduced osteosarcoma cell proliferation and increased NELL1 and NELL2 expression in vivo . Finally, rescue experiments showed that knockdown of NELL1 or NELL2 reversed the inhibitory effects of ANO5 knockdown on osteosarcoma cell proliferation and migration. These results demonstrated that upregulation of ANO5 promoted osteosarcoma development by decreasing the stability of the NELL1 and NELL2 proteins and that ANO5 may be an effective target for the treatment of osteosarcoma.

ANO4 Expression Is a Potential Prognostic Biomarker in Non-Metastasized Clear Cell Renal Cell Carcinoma

“…According to research by Pan et al ., osteosarcomas express ANO5 , a pro-tumorigenic factor that increases tumor size, grade, and metastasis. The instability and destruction of nel-like proteins 1 and 2 enable such activity [ 66 ]. ANO5 expression is scarce in healthy pancreatic tissue, but it is elevated in pancreatic cancer, where it contributes to the disease’s proliferation and migration [ 67 ].…”

Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?

“…Furthermore, ANO9 knockdown sensitises pancreatic cancer cells to EGFR-targeted treatment with erlotinib [ 148 ]. Similarly, ANO5 has also been studied for its role in proliferation and migration in pancreatic cancer [ 143 ], thyroid cancer [ 144 ], and osteosarcoma [ 145 ] models in vitro, and ANO7 has been associated with poor prognosis in prostate cancer [ 147 ] ( Table 2 ). This suggests that other ANOs besides ANO1 may play similar roles in cancer cell progression.…”

Ca2+-Activated Chloride Channels and Phospholipid Scramblases

“…Seo et al identified a new blocker for TMEM16A showing a proapoptic effect on lung cancer cells [36]. The pharmacology of the TMEM16 protein is still rudimental; very few specific blockers or agonists have been reported, and for most of them, the molecular mechanisms of blockage or activation are still unknown [37,38].…”