論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	Identification of ANT2 as a Druggable Target for Endocrine-Resistant ERα-Positive Breast Cancer.
掲載誌名	正式名：International journal of molecular sciences 略　 称：Int J Mol Sci ISSNコード：14220067/14220067
掲載区分	国外
巻・号・頁	27(8),pp.3704
著者・共著者	Erika Iguchi, Motoki Watanabe, Kaito Kobayashi, Shogen Boku, Wataru Nishio, Chikage Kato, Midori Morita, Koichi Sakaguchi, Michihiro Mutoh, Tomoshi Kameda, Yasuto Naoi
発行年月	2026/04
概要	Endocrine therapy is the mainstay for estrogen receptor (ER) α-positive breast cancer (BC), yet many patients display acquired resistance. We then screened natural compounds using human ERα-positive BC cells and identified perillyl alcohol (POH), a monoterpene from perilla, that reduces ERα protein levels. Chemoproteome analysis using POH-immobilized nanomagnetic beads revealed adenine nucleotide translocase 2 (ANT2), a mitochondrial inner membrane protein, as a direct target of POH. Molecular dynamics (MD) simulations predicted POH binding to the central pore of ANT2, which functions in ATP transport. ANT2 depletion reduced ERα levels, and public datasets indicate that high ANT2 expression correlates with poor prognosis in ERα-positive BC. POH also inhibited the growth of Tamoxifen- and Fulvestrant-resistant BC cells. RNA sequencing showed that fatty acid elongation-related genes were upregulated in Fulvestrant-resistant cells but downregulated by ANT2 depletion. Both ANT2 depletion and POH treatment led to the accumulation of intracellular lipid droplets in Fulvestrant-resistant cells, consistent with impaired fatty acid elongation. Finally, in silico screening using MD simulations identified venetoclax and nystatin as potential ANT2 pore binders. Both compounds reduced ERα levels in ERα-positive BC cells and increased lipid droplet formation in Fulvestrant-resistant cells. These findings highlight ANT2 as a druggable target against endocrine-resistant BC.
DOI	10.3390/ijms27083704
PMID	42074342