2019 Vol. 10, No. 11

While p53 is widely considered as a tumor suppressor that induces cell apoptosis upon severe DNA damage, Ge Y et al.report that p53 acts to promote the proliferation of ALT (telomerase negative) cancer cells by suppressing the apoptosis through activation of AKT.The pro-or anti-apoptosis function of p53 is dependent upon its concentration in cells. ALT cancers express a low level of p53 that is insufficient to initiate the transcription of apoptosis-related genes, but is able to stimulate the expression of mTORC2 that activates AKT. Therefore, inhibition of p53 and/or AKT has a potential as therapeutics for specifically targeting ALT cancers that bear a high load of apoptotic stress.
Professor Yongjia Duan:a distinguished plant pathologist and agricultural educator
Fei Du, Wei-Ping Deng, Xia-Hong He, Hong Cai, You-Yong Zhu
2019, 10(11): 779-782. doi: 10.1007/s13238-019-0616-1
The evolving CRISPR technology
Meng Yan, Jinsong Li
2019, 10(11): 783-786. doi: 10.1007/s13238-019-0645-9
Phage display screening of therapeutic peptide for cancer targeting and therapy
Phei Er Saw, Er-Wei Song
2019, 10(11): 787-807. doi: 10.1007/s13238-019-0639-7
Recently, phage display technology has been announced as the recipient of Nobel Prize in Chemistry 2018. Phage display technique allows high affinity target-binding peptides to be selected from a complex mixture pool of billions of displayed peptides on phage in a combinatorial library and could be further enriched through the biopanning process; proving to be a powerful technique in the screening of peptide with high affinity and selectivity. In this review, we will first discuss the modifications in phage display techniques used to isolate various cancer-specific ligands by in situ, in vitro, in vivo, and ex vivo screening methods. We will then discuss prominent examples of solid tumor targeting-peptides; namely peptide targeting tumor vasculature, tumor microenvironment (TME) and overexpressed receptors on cancer cells identified through phage display screening. We will also discuss the current challenges and future outlook for targeting peptidebased therapeutics in the clinics.
Research article
Inhibition of p53 and/or AKT as a new therapeutic approach specifically targeting ALT cancers
Yuanlong Ge, Shu Wu, Zepeng Zhang, Xiaocui Li, Feng Li, Siyu Yan, Haiying Liu, Junjiu Huang, Yong Zhao
2019, 10(11): 808-824. doi: 10.1007/s13238-019-0634-z
While the majority of all human cancers counteract telomere shortening by expressing telomerase,∼15% of all cancers maintain telomere length by a telomeraseindependent mechanism known as alternative lengthening of telomeres (ALT). Here, we show that high load of intrinsic DNA damage is present in ALT cancer cells, leading to apoptosis stress by activating p53-independent, but JNK/c-Myc-dependent apoptotic pathway. Notably, ALT cells expressing wild-type p53 show much lower apoptosis than p53-deficient ALT cells. Mechanistically, we find that intrinsic DNA damage in ALT cells induces low level of p53 that is insufficient to initiate the transcription of apoptosis-related genes, but is sufficient to stimulate the expression of key components of mTORC2 (mTOR and Rictor), which in turn leads to phosphorylation of AKT. Activated AKT (p-AKT) thereby stimulates downstream anti-apoptotic events. Therefore, p53 and AKT are the key factors that suppress spontaneous apoptosis in ALT cells. Indeed, inhibition of p53 or AKT selectively induces rapid death of ALT cells in vitro, and p53 inhibitor severely suppresses the growth of ALT-cell xenograft tumors in mice. These findings reveal a previously unrecognized function of p53 in antiapoptosis and identify that the inhibition of p53 or AKT has a potential as therapeutics for specifically targeting ALT cancers.
Characterization of oogonia stem cells in mice by Fragilis
Xiaoyan Sheng, Chenglei Tian, Linlin Liu, Lingling Wang, Xiaoying Ye, Jie Li, Ming Zeng, Lin Liu
2019, 10(11): 825-831. doi: 10.1007/s13238-019-00654-0
Multiple sgRNAs facilitate base editingmediated i-stop to induce complete and precise gene disruption
Kun Jia, Zongyang Lu, Fei Zhou, Zhiqi Xiong, Rui Zhang, Zhiwei Liu, Yu'e Ma, Lei He, Cong Li, Zhen Zhu, Dejing Pan, Zhengxing Lian
2019, 10(11): 832-839. doi: 10.1007/s13238-019-0611-6
Analysis of VISTA expression and function in renal cell carcinoma highlights VISTA as a potential target for immunotherapy
Shanjuan Hong, Qing Yuan, Haizhui Xia, Genzhen Zhu, Yu Feng, Qiang Wang, Zhiyin Zhang, Wei He, Jian Lu, Chen Dong, Ling Ni
2019, 10(11): 840-845. doi: 10.1007/s13238-019-0642-z
DJ-1 is dispensable for human stem cell homeostasis
Fang Cheng, Si Wang, Moshi Song, Zunpeng Liu, Ping Liu, Lei Wang, Yanjiang Wang, Qian Zhao, Kaowen Yan, Piu Chan, Weiqi Zhang, Jing Qu, Guang-Hui Liu
2019, 10(11): 846-853. doi: 10.1007/s13238-019-00659-9