Article
Pharmacology & Pharmacy
Barbara Pinto, Pedro Novais, Ana C. Henriques, Juliana Carvalho-Tavares, Patricia M. A. Silva, Hassan Bousbaa
Summary: This study investigated the combination of the apoptosis activator Navitoclax and the antimitotic BI2536 to overcome slippage and enhance cell death in mitosis. The results showed that the combination significantly reduced slippage and accelerated cell death, confirming the potential of apoptosis potentiators in circumventing resistance to antimitotics. The synergy/additive effect observed in vitro warrants further clinical research for the BI2536/Navitoclax combination.
Article
Cell Biology
Sadia Sarwar, Viacheslav M. Morozov, Hamsa Purayil, Yehia Daaka, Alexander M. Ishov
Summary: Androgen ablation therapy is the standard treatment for newly diagnosed prostate cancer patients. However, the relapse of castration-resistant prostate cancer (CRPC) often leads to metastasis and disease lethality. Current therapies for metastatic CRPC are limited due to resistance to Taxanes. In this study, we found that inhibition of the mitotic checkpoint kinase Mps1 enhances the efficacy of Taxanes treatment, providing a potential new therapeutic target for managing therapy-resistant metastatic CRPC.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Eric M. C. Britigan, Jun Wan, Daniel K. Sam, Sarah E. Copeland, Amber L. Lasek, Laura C. F. Hrycyniak, Lei Wang, Anjon Audhya, Mark E. Burkard, Avtar Roopra, Beth A. Weaver
Summary: The increased expression of Aurora B protein reduces its kinase activity and causes defects in mitosis. The complexes of Aurora B and its binding partner INCENP achieve Aurora B activation through autophosphorylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Haiyu Song, Eun Ho Kim, Jihee Hong, Dasom Gwon, Jee Won Kim, Gyu-Un Bae, Chang-Young Jang
Summary: The centrosome forms a bipolar spindle during mitosis for faithful chromosome segregation. The DNA damage response (DDR) induces programmed spindle multipolarity and death in mitosis to prevent inheritance of DNA damage. Hornerin acts as a link between DDR and death in mitosis by forming a complex with checkpoint kinase 1 (Chk1) and polo-like kinase 1 (Plk1) to mediate phosphorylation at the polo-box domain (PBD) of Plk1. Hornerin mediates DDR-induced premature centriole disengagement through phosphorylation of Plk1 PBD, leading to spindle multipolarity. This study reveals the mechanism of how DDR eliminates mitotic cells with DNA damage to maintain genome integrity.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Wonkyung Oh, Ting Ting Wu, Seo-Yeon Jeong, Ho Jin You, Jung-Hee Lee
Summary: CtIP plays a critical role in regulating mitosis by interacting with TPX2 to control spindle dynamics and regulate the concentration of Aurora A and microtubule intensity at the spindle poles. Depletion of CtIP may lead to improper execution of mitosis and result in chromosomal instability.
Article
Biochemistry & Molecular Biology
Fiorella Faienza, Federica Polverino, Girish Rajendraprasad, Giacomo Milletti, Zehan Hu, Barbara Colella, Deborah Gargano, Flavie Strappazzon, Salvatore Rizza, Mette Vixo Vistesen, Yonglun Luo, Manuela Antonioli, Valentina Cianfanelli, Caterina Ferraina, Gian Maria Fimia, Giuseppe Filomeni, Daniela De Zio, Joern Dengjel, Marin Barisic, Giulia Guarguaglini, Sabrina Di Bartolomeo, Francesco Cecconi
Summary: AMBRA1 is a key factor for nervous system development, primarily associated with autophagy and cell proliferation control. This study reveals that AMBRA1 is phosphorylated during mitosis and is critical for spindle function and orientation, driven by NUMA1 protein. The localization and dynamics of NUMA1 are dependent on AMBRA1 presence, phosphorylation, and binding ability. These findings suggest an additional role of AMBRA1 in tissue morphogenesis and differentiation, which could have implications for development and cancer oncogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Physiology
Mathew Bloomfield, Jing Chen, Daniela Cimini
Summary: This study found that differences in mitotic duration can be explained by variations in spindle microtubule densities and sizes of the cell, spindle, and spindle poles. The study suggests that spindle size does not always scale with cell size in mammalian cells, and cell size alone is not sufficient to explain differences in metaphase duration. Only when considering a number of spindle architectural features along with cell size can the kinetics of SAC silencing, and hence mitotic duration, be explained in different clones.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biology
Alex F. Thompson, Patrick R. Blackburn, Noah S. Arons, Sarah N. Stevens, Dusica Babovic-Vuksanovic, Jane B. Lian, Eric W. Klee, Jason Stumpff
Summary: This study reveals that mutations in KIF22 disrupt chromosome segregation in anaphase, leading to reduced proliferation and abnormal cell morphology. It demonstrates the significance of regulating KIF22 activity and maintaining force balance in anaphase.
Article
Oncology
Jose Thaiparambil, Chandra S. Amara, Subrata Sen, Nagireddy Putluri, Randa El-Zein
Summary: The exposure to cigarette smoke can induce centrosome amplification and clustering in lung epithelial cells, which may contribute to lung carcinogenesis. The cyclin D2-mediated centrosome clustering pathway is critical for mitosis and its inhibition can lead to cell death.
Article
Microbiology
Ramiro Tomasina, Fabiana C. Gonzalez, Erica S. Martins-Duarte, Philippe Bastin, Mathieu Gissot, Maria E. Francia
Summary: Centrosomes are crucial for cell division and formation of the mitotic spindle. This study reveals the important role of the inner core protein TgCep250L1 in Toxoplasma gondii cell division, as its absence leads to nuclear segregation defects and failure to assemble the mitotic spindle.
Article
Cell Biology
Inmaculada Ayala, Antonino Colanzi
Summary: The Golgi complex plays a central role in secretory traffic and can form a structure called the Golgi ribbon. The balanced formation and cleavage of membrane tubules connecting the stacks are crucial for cell division and spindle formation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Imge Ozugergin, Alisa Piekny
Summary: Cytokinesis, the process of physically dividing a cell into two daughters, has been extensively studied in vitro and early embryos, but its regulation in different animal cell types and developmental contexts remains poorly understood. Recent studies have revealed striking differences in the regulation of cytokinesis between different cell types and organisms, including diverse threshold requirements for structural components and different mechanisms of regulation. This review focuses on these differences, particularly in pathways independent of the mitotic spindle, and associated with the cortex, kinetochores, or chromatin.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Diana Campos-Iglesias, Julia M. Fraile, Gabriel Bretones, Alejandro A. Montero, Elena Bonzon-Kulichenko, Jesus Vazquez, Carlos Lopez-Otin, Jose M. P. Freije
Summary: USP49 deubiquitinase is identified as a novel regulator of the spindle checkpoint. Loss of USP49 impairs proliferation and increases aneuploidy in cancer cell lines. USP49-depleted cells can overcome SAC-induced arrest in presence of nocodazole.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Dilara Koyuncu, Utsav Sharma, Erik T. Goka, Marc E. Lippman
Summary: The study revealed that SAC genes were elevated in breast cancer, with BUB1B showing the most significant change. Overexpression of BUB1B was associated with decreased overall survival. Reduction of BUB1B expression led to decreased viability and clonogenicity in BrCa cell lines, increased apoptosis and cell death, as well as chromosomal abnormalities.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Oncology
Saki Ota, Yui Tanaka, Ryuji Yasutake, Yuki Ikeda, Ryuzaburo Yuki, Yuji Nakayama, Youhei Saito
Summary: Heat shock can lead to protein denaturation and inactivation in cells. Previous research showed that mild heat shock at 42°C can delay mitotic progression by activating the spindle assembly checkpoint (SAC). However, it is unclear if SAC activation occurs at temperatures higher than 42°C. This study demonstrated that a high temperature of 44°C before mitotic entry caused a prolonged mitotic delay, which was shortened by the SAC inhibitor, AZ3146. Mitotic slippage and multinucleation were observed at 44°C but not at 42°C heat shock. Heat shock at 44°C also reduced the kinetochore localization of MAD2, an important protein for mitotic checkpoint activation, in nocodazole-arrested mitotic cells. These findings suggest that heat shock at 44°C can cause SAC inactivation even after full activation and may lead to mitotic slippage and multinucleation. This has implications for cancer malignancy as mitotic slippage can cause drug resistance and chromosomal instability.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yuping Chen, Jinhuan Wu, Guang Liang, Guohe Geng, Fei Zhao, Ping Yin, Somaira Nowsheen, Chengming Wu, Yunhui Li, Lei Li, Wootae Kim, Qin Zhou, Jinzhou Huang, Jiaqi Liu, Chao Zhang, Guijie Guo, Min Deng, Xinyi Tu, Xiumei Gao, Zhongmin Liu, Yihan Chen, Zhenkun Lou, Kuntian Luo, Jian Yuan
Article
Biochemistry & Molecular Biology
Jeaho Lim, Juyoung Son, Jaewook Ryu, Ja-Eun Kim
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Multidisciplinary Sciences
Qin Zhou, Jinzhou Huang, Chao Zhang, Fei Zhao, Wootae Kim, Xinyi Tu, Yong Zhang, Somaira Nowsheen, Qian Zhu, Min Deng, Yuping Chen, Bo Qin, Kuntian Luo, Baohua Liu, Zhenkun Lou, Robert W. Mutter, Jian Yuan
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Jinzhou Huang, Qin Zhou, Ming Gao, Somaira Nowsheen, Fei Zhao, Wootae Kim, Qian Zhu, Yusuke Kojima, Ping Yin, Yong Zhang, Guijie Guo, Xinyi Tu, Min Deng, Kuntian Luo, Bo Qin, Yuichi Machida, Zhenkun Lou
Article
Multidisciplinary Sciences
Ming Gao, Guijie Guo, Jinzhou Huang, Jake A. Kloeber, Fei Zhao, Min Deng, Xinyi Tu, Wootae Kim, Qin Zhou, Chao Zhang, Ping Yin, Kuntian Luo, Zhenkun Lou
NATURE COMMUNICATIONS
(2020)
Letter
Hematology
Shouhai Zhu, Zhihong Chen, Dan Jiang, Ruiheng Wang, Xiaoyan Cheng, Dan Li, Qiongyu Xv, Fei Zhao, Wootae Kim, Guijie Guo, Chunjun Zhao, Zhenkun Lou, Han Liu
Article
Biochemistry & Molecular Biology
Ming Gao, Guijie Guo, Jinzhou Huang, Xiaonan Hou, Hyoungjun Ham, Wootae Kim, Fei Zhao, Xinyi Tu, Qin Zhou, Chao Zhang, Qian Zhu, Jiaqi Liu, Yuanliang Yan, Zhijie Xu, Ping Yin, Kuntian Luo, John Weroha, Min Deng, Daniel D. Billadeau, Zhenkun Lou
Summary: DOCK7 acts as a critical regulator for replication stress response by promoting RPA stability on chromatin. Additionally, overexpression of DOCK7 in ovarian cancer and depletion of DOCK7 in cancer cells sensitizes them to camptothecin, highlighting potential therapeutic targets for overcoming chemoresistance.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Lifeng Chen, Jing Hou, Xiangyu Zeng, Qiang Guo, Min Deng, Jake A. Kloeber, Xinyi Tu, Fei Zhao, Zheming Wu, Jinzhou Huang, Kuntian Luo, Wootae Kim, Zhenkun Lou
Summary: PARP inhibitors induce HR deficiency and increase cancer cell sensitivity to treatment, while LRRK2 inhibitors can increase ovarian cancer cell sensitivity to Olaparib and are associated with HR.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Genetics & Heredity
Wootae Kim, Fei Zhao, Huanyao Gao, Sisi Qin, Jing Hou, Min Deng, Jake A. Kloeber, Jinzhou Huang, Qin Zhou, Guijie Guo, Ming Gao, Xiangyu Zeng, Shouhai Zhu, Xinyi Tu, Zheming Wu, Yong Zhang, Ping Yin, Scott H. Kaufmann, Kuntian Luo, Zhenkun Lou
Summary: This study identifies the deubiquitinating enzyme USP13 as a key regulator of TopBP1, stabilizing it and coordinating the replication stress response. High expression of USP13 enhances cancer cell chemoresistance and correlates with poor prognosis in cancer patients.
Article
Biotechnology & Applied Microbiology
Sisi Qin, James N. Ingle, Wootae Kim, Huanyao Gao, Richard M. Weinshilboum, Liewei Wang
Summary: The study identified potential pathways, including ribosome and AMP-activated protein kinase (AMPK) signaling, regulated by ZNF423 or ZNF423 rs9940645 SNP. The findings suggest that AMPK signaling is modulated by the ZNF423 rs9940645 SNP and may affect metformin response in breast cancer, potentially serving as a biomarker for personalized metformin treatment.
PHARMACOGENETICS AND GENOMICS
(2021)
Article
Multidisciplinary Sciences
Guijie Guo, Ming Gao, Xiaochen Gao, Bibo Zhu, Jinzhou Huang, Xinyi Tu, Wootae Kim, Fei Zhao, Qin Zhou, Shouhai Zhu, Zheming Wu, Yuanliang Yan, Yong Zhang, Xiangyu Zeng, Qian Zhu, Ping Yin, Kuntian Luo, Jie Sun, Min Deng, Zhenkun Lou
Summary: The study reveals that RIG-I is recruited to double-stranded breaks, suppressing non-homologous end joining and compromising DNA repair, while XRCC4 plays a crucial role in RIG-I immune signaling. This reciprocal regulation uncovers a new function of RIG-I in suppressing virus integration and DNA repair, while endowing XRCC4 with a pivotal role in enhancing innate immune response.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Fei Zhao, Wootae Kim, Huanyao Gao, Chao Liu, Yong Zhang, Yuping Chen, Min Deng, Qin Zhou, Jinzhou Huang, Qi Hu, Shih-Hsun Chen, Somaira Nowsheen, Jake A. Kloeber, Bo Qin, Ping Yin, Xinyi Tu, Guijie Guo, Sisi Qin, Chao Zhang, Ming Gao, Kuntian Luo, Yilun Liu, Zhenkun Lou, Jian Yuan
Summary: ASTE1, as a downstream effector of the shieldin complex, cleaves single-stranded and 3' overhang DNA to promote shieldin-dependent non-homologous end-joining, leading to impaired DSB repair and resistance to PARP inhibitors in BRCA1-deficient cells.
NATURE CELL BIOLOGY
(2021)
Article
Oncology
Yong Zhang, Qifan Yang, Xiangyu Zeng, Manxiang Wang, Shuang Dong, Bin Yang, Xinyi Tu, Ting Wei, Wenzhuan Xie, Chao Zhang, Qiang Guo, Jake A. Kloeber, Yueyu Cao, Guijie Guo, Qin Zhou, Fei Zhao, Jinzhou Huang, Li Liu, Kai Zhang, Mingwei Wang, Ping Yin, Kuntian Luo, Min Deng, Wootae Kim, Jing Hou, Yu Shi, Qian Zhu, Lifeng Chen, Sheng Hu, Junqiu Yue, Guoliang Pi, Zhenkun Lou
Summary: The study found that tumors with MET amplification are resistant to immune checkpoint blockade (ICB) therapy, likely due to reduced levels of STING and antitumor T-cell infiltration. It also revealed that the oncogenic MET signaling pathway downregulates tumor cell STING expression through phosphorylation of UPF1 and modulation of the 3'-UTR length of STING. The efficiency of ICB in MET amplification can be improved by inhibiting MET, suggesting a potential combination therapy for patients with this condition.
Review
Biochemistry & Molecular Biology
Jaeyoung Moon, Ichiwa Kitty, Kusuma Renata, Sisi Qin, Fei Zhao, Wootae Kim
Summary: DNA damage has both positive and negative effects on cancer cells. It exacerbates gene mutation frequency and cancer risk, but it also makes cancer cells more sensitive to chemotherapy or radiotherapy. Inhibitors targeting key enzymes in the DNA repair pathway can induce synthetic lethality with cancer therapeutics. This study reviews the general pathways involved in DNA repair and potential protein targets for cancer therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sisi Qin, Ichiwa Kitty, Yalan Hao, Fei Zhao, Wootae Kim
Summary: DNA double-strand breaks (DSBs) are the most lethal DNA damages that result in severe genome instability. Phosphorylation, which is one of the most important protein post-translation modifications, plays a vital role in regulating DSB repair. Kinases and phosphatases coordinate in DSB repair by adding or removing phosphate groups from various proteins. Understanding the function of kinases and phosphatases in DSBs repair is crucial for comprehending their role in cancer development and therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
