Physiological role of DAB2IP in regulating the activity of glycolysis in prostate cancer

• DOI: 10.1096/fasebj.30.1_supplement.1099.22
• Publication Date: 2023-11-26T16:30:36Z
• Authors: CHIA‐YANG LI; Jocelyn Jea; Rey‐Chen Pong; Jichen Yang; Guanghua Xiao; David A Boothman; Jer‐Tsong Hsieh
• Keywords: Anaerobic glycolysis; Hexokinase; Warburg Effect

Cancer cells frequently display high rates of aerobic glycolysis (the Warburg effect) in comparison to their nontransformed counterparts. Activated oncogenes and loss tumor suppressors turn alter metabolism induce glycolysis. Here we report that DOC-2/DAB2 interactive protein (DAB2IP), a suppressor gene, decreases the glycolytic activity prostate cancer cell. In addition, DAB2IP inhibits expression hexokinase 2 (HK-II) which catalyzes phosphorylation glucose first step Although molecular mechanisms underlying regulation remains not completely clear, previous studies indicated PI3K-AKT signaling pathway plays an important role regulating cell metabolism. its downstream effector, c-MYC is also critical regulate HK-II expression. Our experimental results showed Akt c-MYC. We speculated inhibition by may be through activity. Support or Funding Information The Ministry Science Technology(MOST) Taiwan under grant no. 104-2320-B-037 -028 cells. (A) Glycolytic capacity was determined Seahorse analyzer. Extracellular acidification rate (ECAR) based on lactic acid formation during Data level ECAR cells, (B) LAPC4 CON/LAPC4 KD; (C) C4-2 NEO/C4-2 D2. (D) Statistic (**P <0.01). (E) Hexokinase (F) lactate. (*P <0.05; **P levels CON/KD NEO/D2 were real-time PCR <0.05) western blot. Transient transfected plasmid corresponding empty vector control into KD, PC3, for 24hrs. examined PCR. promoter reporter assay. <0.01) related growth after addition starved 24hrs using minimal medium. After starvation, 25 mM added another 24 hrs then trypan blue exclusion as well analyzed Cells kept medium starvation control. affects chemosensitivity Prostate lines, LNCaP DU145, with shRNA (scrambled control, SC). blot MTT assay treated doxorubicin (DOX) paclitaxel (PTX) 48h. viability assayed effect PI3K/AKT expressions phospho-AKT AKT CON/KD, PC3 LY294002 MYC DAB2IP, MYC, human samples benign primary samples. MYCafter transient DAB2IP. specimens. Gene from TCGA RNA-seq data many types cancers. Immunohistochemical staining tissue microarrays. Histogram tissue, naive cancer, lymph node (LN)-metastatic