The proliferation of cells and growth of individuals are closely related to mitosis and relies on functionally precise mitosis to correctly transmit genetic information to daughter cells. Mitotic cell death occurs when cells are unable to complete mitosis due to extensive DNA damages, disruption of the mitotic machineries, and/or failure of mitotic checkpoints, thereby reducing the risk of genomic abnormalities in daughter cells and avoiding disease development. However, many cancer cells displaying a high degree of centrosome amplification and/or spindle defects are vulnerable to generate mitotic aberrations. To survive, these cells acquire strategies to attenuate the induction of mitotic cell death, allowing the development of advanced malignancy, recurrence and drug resistance. Thus, modulation of mitotic cell death controls cancer development and is an attractive intervention strategy for cancer therapy.
By using cell biology methods in cultured cell models, we systematically dissect how cells respond to mitotic failures and identify and characterize the cellular and molecular mechanisms for controlling mitotic cell death and survival. Through these studies, we can further understand the key mechanism(s) in cancer development and identify potential therapeutic targets for cancer treatment.
Kuo HH, Su ZR, Chuang JY, and Yih LH*. Heat shock factor 1 suppression induces spindle abnormalities and sensitizes cells to antimitotic drugs. Cell Division. 16(1):8.
Fang CT, Kuo HH, Yuan CJ, Yao JS, and Yih LH*. Mdivi-1 induces spindle abnormalities and augments taxol cytotoxicity in MDA-MB-231 cells. Cell Death Discovery. 7(1):118. 2021.
Fang CT, Kuo HH, Hsu SC, and Yih LH*. HSP70 regulates Eg5 distribution within the mitotic spindle and modulates the cytotoxicity of Eg5 inhibitors. Cell Death & Disease. 11(8):715. 2020.
Lin TC, Kuo HH, Wu YC, Pan TS, and Yih LH*. Phosphatidylinositol-5-phosphate 4-kinase gamma accumulates at the spindle pole and prevents microtubule depolymerization. Cell Division. 14(9). 2019.
Fang CT, Kuo HH, Hsu SC, and Yih LH*. HSP70 is required for the proper assembly of pericentriolar material and function of mitotic centrosomes. Cell Division. 14(4). 2019.
Fang CT, Kuo HH, Pan TS, Yu FC, and Yih LH*. HSP70 regulates the function of mitotic centrosomes. Cell Mol Life Sci. 73(20):3949-60. 2016.
Kuo HH, Kakadiya R, Wu YC, Chuang CY, Su TL, TC Lee, YW Lin, and Yih LH*. Derivatives of 6-cinnamamido-quinoline-4-carboxamide impair lysosome function and induce apoptosis. Oncotarget. 7(25):38078-38090. 2016.
Liou JS, Wu YC, Yen WY, Tang YS, Kakadiya RB, Su TL, and Yih LH*. Inhibition of autophagy enhances DNA damage-induced apoptosis by disrupting CHK1-dependent S phase arrest. Toxicol Appl Pharmacol. 278(3):249-58. 2014.
Chen YJ, Lai KC, Kuo HH, Chow LP, Yih LH*, and Lee TC*. HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide. Arch Toxicol. 88(9):1711-23. 2014. (Co-corresponding)
Yih LH*, Hsu NC, Wu YC, Yen WY, and Kuo HH. Inhibition of AKT enhances mitotic cell apoptosis induced by arsenic trioxide. Toxicol Appl Pharmacol. 267(3):228-37. 2013.