Article
Biochemistry & Molecular Biology
Yuqi Yang, Qiu-Xu Teng, Zhuo-Xun Wu, Jing-Quan Wang, Zi-Ning Lei, Sabrina Lusvarghi, Suresh Ambudkar, Ning Ji, Zhe-Sheng Chen
Summary: Overexpression of ABCBC1 significantly reduces sensitivity to OTS964 in cells and tumors, which can be antagonized by verapamil. OTS964 also induces resistance to other ABCBC1 substrate-drugs by stimulating ATPase activity and upregulating ABCBC1 expression levels, with comparable affinity to the substrate-binding site of human ABCBC1 protein.
Review
Cell Biology
Ziping Han, Lingzhi Li, Yuyou Huang, Haiping Zhao, Yumin Luo
Summary: Accumulating evidence suggests PBK/TOPK plays a role in mitosis and cell-cycle progression, with potential therapeutic implications in cancer. However, further research is needed to understand the applicability of PBK/TOPK inhibitors in clinical practice, given their overexpression in normal and pathological proliferative cells.
Article
Chemistry, Physical
He Wang, Xun Zhu, Yizhen Zhao, Yongjian Zang, Jianwen Zhang, Ying Kang, Zhiwei Yang, Peng Lin, Lei Zhang, Shengli Zhang
Summary: This study investigated the micromechanism of TOPK, a potential target for cancer therapy, through modeling and simulation. The results showed that the ENI motif of the NTPM is regulated by the N-C interaction zone, and mutations at specific residues promote conformational changes and phosphorylation. Furthermore, allosteric effects induce structural changes that are important for activation or binding. These findings provide insights for designing inhibitors and understanding the regulatory mechanisms of TOPK monomers.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Harold A. Chinyama, Li Wei, Ntlotlang Mokgautsi, Bashir Lawal, Alexander T. H. Wu, Hsu-Shan Huang
Summary: Glioblastoma multiforme (GBM) is a deadly primary brain tumor with limited treatment options. Dysregulated cell cycle progression contributes to the rapid growth of GBM. Overexpression of CDK1, PBK, and CHEK1 is associated with chemoradioresistance and poor prognosis in GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jinxin Li, Huimin Sun, Meiling Fu, Zeyuan Zheng, Chunlan Xu, Kunao Yang, Yankuo Liu, Zuodong Xuan, Yang Bai, Jianzhong Zheng, Yue Zhao, Zhiyuan Shi, Chen Shao
Summary: This study demonstrates that high expression of TOPK in RCC promotes PD-L1 expression by activating ERK2 and TGF-beta/Smad pathways. TOPK is also shown to inhibit CD8(+) T cell infiltration and function, promoting immune escape in RCC. Inhibition of TOPK enhances CD8(+) T cell infiltration, activation, anti-PD-L1 therapeutic efficacy, and synergistically enhances anti-RCC immune response.
Article
Cell Biology
Hanlin Ma, Fang Han, Xiaohui Yan, Gonghua Qi, Yingwei Li, Rongrong Li, Shi Yan, Cunzhong Yuan, Kun Song, Beihua Kong
Summary: Cervical cancer is the fourth most common cancer in women globally, and the overexpression of PBK in cervical cancer tissues promotes proliferation, metastasis, and cisplatin resistance of cancer cells through the ERK/c-Myc signaling pathway. Inhibition of PBK with OTS514 shows promising results in suppressing tumor growth and enhancing chemosensitivity. Further studies on PBK as a molecular target for cervical cancer treatment are warranted.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Editorial Material
Chemistry, Medicinal
Mark Klein
Summary: Cyclin-dependent kinases (CDKs) have important roles in normal cells and can be targeted for cancer therapy. CDK4 inhibitors have been approved for advanced breast cancer treatment. However, the development of selective inhibitors for individual CDKs is challenging due to the highly conserved ATP-binding site.
Article
Oncology
Yuhao Deng, Huantao Wen, Hanjie Yang, Zhengqiang Zhu, Qiongzhen Huang, Yuewei Bi, Pengfei Wang, Ming Zhou, Jianwei Guan, Wangming Zhang, Min Li
Summary: Medulloblastoma (MB) is the most common malignant brain tumor in pediatrics. Current standard treatment often results in high morbidity, so there is a need for more effective and less toxic therapies. This study identified an upregulated gene (PDZ binding kinase) in MB and found its aberrant expression to be associated with poor clinical outcomes. Targeting this gene with an inhibitor impaired MB cell proliferation and induced apoptosis.
Article
Oncology
Wan-Nien Yu, Heng-Fu Lin, Yi Lee, Wei-Chung Shia, Wen-Wei Sung, Chung-Min Yeh, Yueh-Min Lin
Summary: High PBK expression is associated with a favorable clinical outcome in patients with oral squamous cell carcinoma, especially in advanced-stage disease. PBK can be used as an independent prognostic marker for patients treated with radiotherapy.
ANTICANCER RESEARCH
(2021)
Article
Pathology
Aya Nagano-Matsuo, Satoshi Inoue, Akira Koshino, Akinobu Ota, Kenju Nakao, Masayuki Komura, Hiroyuki Kato, Aya Naiki-Ito, Kawori Watanabe, Yuko Nagayasu, Yoshitaka Hosokawa, Shuji Takiguchi, Kunio Kasugai, Kenji Kasai, Shingo Inaguma, Satoru Takahashi
Summary: High expression of PBK in CRC is significantly associated with favorable survival outcomes for patients, making it a potential prognostic factor. Inhibition of PBK can suppress cellular proliferation of CRC cells, suggesting the potential utility of PBK-targeting therapeutics for treating CRC patients with high PBK expression.
Review
Pharmacology & Pharmacy
Kailin Li, Jieqiong You, Qian Wu, Wen Meng, Qiaojun He, Bo Yang, Chengliang Zhu, Ji Cao
Summary: Synthetic lethality is an effective antitumor strategy that has attracted great attention, with CDKs potentially serving as synthetic lethal factors when combined with certain oncogenes. This provides numerous antitumor treatment options and highlights the prospect of CDK inhibitors as antitumor compounds.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Cell Biology
Lihuan Guan, Karen C. Crasta, Andrea B. Maier
Summary: This review highlights the significance of cellular senescence markers in human peripheral blood cells, summarizes related experiments and detection methods, as well as studies on demographic and clinical characteristics.
AGEING RESEARCH REVIEWS
(2022)
Article
Plant Sciences
Rui-Yi Yang, Jia-Yi Tan, Zhe Liu, Xiao-Ling Shen, Ying-Jie Hu
Summary: The natural lignan LAF from Arctium lappa Linne has been found to inhibit tumor cell growth in vitro and in vivo. However, its role in cell cycle regulation remains unknown.
PHARMACEUTICAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yanting Zhou, Xiandeng Li, Peifang Luo, Huiting Chen, Yan Zhou, Xueting Zheng, Yuan Yin, Haoche Wei, Hongji Liu, Wen Xia, Mingsong Shi, Xiaoan Li
Summary: CDK4/6 is a crucial player in various cancers and a potential target for anticancer drugs. The interaction between abemaciclib and human CDK6 was studied, and C2231-A was identified as a promising candidate compound with significant inhibitory effects on human breast cancer cell lines.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Chuang Li, Yuan Lyu, Caixia Liu, Shaowei Yin
Summary: This study utilized bioinformatics analysis to identify potential key genes associated with ovarian cancer, providing potential diagnostic and therapeutic targets. Through differential gene expression analysis and gene co-expression network analysis, PBK gene was identified to be potentially associated with the pathogenesis and prognosis of ovarian cancer.
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
(2022)