Elucidating the mechanism of resistance to nutrient deprivation and anticancer drugs via TFAP2E in neuroblastoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17566
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Nihon University
• Principal Investigator: NAGASAKI Eri 日本大学, 医学部, 研究医員 (70845354)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 神経芽腫 / 栄養飢餓耐性 / 抗がん剤耐性 / TFAP2E

Outline of Final Research Achievements

We previously reported that depletion of TFAP2E enhanced chemoresistance in neuroblastoma (NB) cells, and that a lower expression TFAP2E level was related to a poor prognosis in patients with NB. In this study, we demonstrated that TFAP2E-depleted NB cells were also resistant to glucose deprivation, and the results of an ATP assay indicated that NB cells acquired resistance to low ATP levels. Furthermore, a microarray analysis showed that the expression of SUSD2 was significantly higher in TFAP2E-depleted NB cells, and a public database analysis showed that the higher expression of SUSD2, which has been reported to confer chemoresistance in other types of cancer, was associated with a poor prognosis in patients with NB. These findings indicated that underexpression of TFAP2E in NB probably promotes chemoresistance through increasing the expression of SUSD2, leading to a poor prognosis.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

神経芽腫の治療成績は集学的治療の発達により著しく改善したが、進行期の神経芽腫では抗がん剤耐性を示す腫瘍細胞が多く存在する。本研究成果から、TFAP2Eの発現低下は栄養飢餓耐性と抗がん剤耐性の両者に関与することが示唆された。将来的には、TFAP2Eの発現を増強させる脱メチル化剤による治療法や、TFAP2Eの下流にある栄養飢餓耐性/抗がん剤耐性に関与する分子を標的とした新規治療薬開発に発展させ、予後の改善に寄与することが期待できると考えられる。