Biallelic loss of FAM46C triggers tumor growth with concomitant activation of Akt signaling in multiple myeloma cells

• DOI: 10.1111/cas.14386
• Publication Date: 2020-03-16T20:14:49Z
• Authors: Jo Kanasugi; Ichiro Hanamura; Akinobu Ota; Sivasundaram Karnan; Vu Quang Lam; Shohei Mizuno; Md Wahiduzzaman; Md Lutfur Rahman; Toshinori Hyodo; Hiroyuki Konishi; Shinobu Tsuzuki; Yoshitaka Hosokawa; Akiyoshi Takami
• Keywords: Concomitant

Abstract Loss of heterozygosity or mutation the family with sequence similarity 46, member C ( FAM46C ) gene on chromosome band 1p12 is associated shorter overall survival patients multiple myeloma (MM). In this study, using human MM cell lines (KMS‐11, OCI‐My5, and ANBL‐6), we generated −/− clones examined effect disruption cellular signaling. Cell proliferation assays showed increased clonogenicity KMS‐11 cells compared to WT cells. Xenograft experiments significantly mice harboring cell‐derived tumors than tumors. Notably, levels phosphorylated Akt its substrates both in vitro vivo addition, caspase activities decreased Results set enrichment analysis that loss activated serum‐responsive genes while inactivating phosphatase tensin homolog (PTEN)‐related genes. Mechanistically, PTEN activity, number apoptotic cells, activities. PF‐04691502, a selective PI3K inhibitor, suppressed augmented phosphorylation substrate FoxO3a. Treatment afuresertib (a specific inhibitor) combination bortezomib additively survival. Collectively, study first report triggers concomitant activation PI3K‐Akt signaling pathway, which might be therapeutic target for abnormalities gene.