Development of stratified diagnostic method of breast cancer and elucidation of the regulatory mechanism of RNA based on Txnip research

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07347
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Tenri Health Care University
• Principal Investigator: Masutani Hiroshi 天理医療大学, 医療学部, 教授 (50252523)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Txnip / breast cancer / triple negative / Autophagy

Outline of Final Research Achievements

We investigated the expression of thioredoxin interacting protein (Txnip) in breast cancer tissues in collaboration with Tenri Hospital. We showed that Txnip localizes in the membrane-associated region in some triple negative type breast cancer tissues. We are analyzing Txnip anchoring molecules by proximity labeling. We identified Txnip-induced several important signal regulating molecules such as DNA methylating enzyme and a component of the BRCA1 complex. We also showed that Txnip causes growth suppression and autophagy in Mixed lineage leukemia (MLL) cells and enhances ABT263 (Navitoclax)-induced cell death. These results provide a clue to elucidate the molecular mechanism of anti-cancer action of Txnip and to develop an approach against breast cancer and MLL.

Free Research Field

病態医化学

Academic Significance and Societal Importance of the Research Achievements

乳癌のサブタイプの中で治療抵抗性であるtriple negativeタイプを積極的に診断する指標はなく、的確な治療法選択のために、適切な層別指標の開発が望まれている。今回、細胞膜付近にTxnipと相互作用するアンカー因子の存在が示唆された。また、Txnip過剰発現により発現誘導される因子を同定した。これらの因子は、Txnipの発癌抑制機構を明らかにし、乳癌の層別診断法、治療法の開発に資すると考えられる。さらに、Txnipによる増殖制御やオートファジー制御分子機構の解明が難治性のMixed lineage leukemia (MLL) 急性骨髄性白血病の治療に応用できる可能性を示唆する。