SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7

Abstract

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

Integrating single-cell and bulk sequencing data to identify glycosylation-based genes in non-alcoholic fatty liver disease-associated hepatocellular carcinoma

“…This suggests the need to go further to explore the effects of possible glycosylation modifications on SOCS2 function and activity. SAPCD2, as an oncogene, can promote cell proliferation and tumor development, potentially affecting pathways such as PI3K/Akt, MAPK, and Hippo, although its direct effect on immune checkpoints is not yet clear ( Zhang et al, 2022 ). The four glycosylation sites at the extracellular N-terminal end of RAMP3 play important physiological roles in binding to other proteins ( Flahaut et al, 2003 ).…”

Integrative analysis of lysine acetylation-related genes and identification of a novel prognostic model for oral squamous cell carcinoma

“…NK2 homeobox 3 (NKX2-3) has been reported as a prognostic factor in head and neck squamous cell carcinoma (HNSCC) ( Huang L. et al, 2021 ; Liu et al, 2021 ). Suppressor APC domain containing neuroblastoma (SAPCD2) ( Zhang et al, 2022 ), has been reported to regulate Yap/Taz, MAPK, and mTOR signaling in various cancers, including colorectal ( Luo et al, 2020 ) and prostate cancer ( Sun et al, 2021 ). Serine peptidase inhibitor Kazal type 7 (SPINK7) has also been proposed as a prognostic factor also a molecular biomarker in HNSCC ( Pennacchiotti et al, 2021 ; Du et al, 2022 ).…”

Self-Assembled Nanocomposite DOX/TPOR4@CB[7]4 for Enhanced Synergistic Photodynamic Therapy and Chemotherapy in Neuroblastoma

“…Neuroblastoma (NB) is an embryonic tumor of the sympathetic system, originating from 8% to 10% of tumors in children. It represents the most prevalent malignant solid neoplasm in infants and young children, ranking as the second most common extracranial malignancy among this age group [ 1 , 2 , 3 ]. Neuroblastoma displays remarkable phenotypic heterogeneity [ 4 ].…”