2018 Vol. 9(8)

Recollection
Investigation on natural resources and species conservation of Ophiocordyceps sinensis, the famous medicinal fungus endemic to the Tibetan Plateau
Wenjing Wang, Ke Wang, Xiaoliang Wang, Ruiheng Yang, Yi Li, Yijian Yao
2018, 9(8): 671-673. doi: 10.1007/s13238-017-0406-6
Abstract:
Review
Revisiting ovarian cancer microenvironment: a friend or a foe?
Boyi Zhang, Fei Chen, Qixia Xu, Liu Han, Jiaqian Xu, Libin Gao, Xiaochen Sun, Yiwen Li, Yan Li, Min Qian, Yu Sun
2018, 9(8): 674-692. doi: 10.1007/s13238-017-0466-7
Abstract:
Development of ovarian cancer involves the co-evolution of neoplastic cells together with the adjacent microenvironment. Steps of malignant progression including primary tumor outgrowth, therapeutic resistance, and distant metastasis are not determined solely by genetic alterations in ovarian cancer cells, but considerably shaped by the fitness advantage conferred by benign components in the ovarian stroma. As the dynamic cancer topography varies drastically during disease progression, heterologous cell types within the tumor microenvironment (TME) can actively determine the pathological track of ovarian cancer. Resembling many other solid tumor types, ovarian malignancy is nurtured by a TME whose dark side may have been overlooked, rather than overestimated. Further, harnessing breakthrough and targeting cures in human ovarian cancer requires insightful understanding of the merits and drawbacks of current treatment modalities, which mainly target transformed cells. Thus, designing novel and precise strategies that both eliminate cancer cells and manipulate the TME is increasingly recognized as a rational avenue to improve therapeutic outcome and prevent disease deterioration of ovarian cancer patients.
Research articles
Hypertonia-linked protein Trak1 functions with mitofusins to promote mitochondrial tethering and fusion
Crystal A. Lee, Lih-Shen Chin, Lian Li
2018, 9(8): 693-716. doi: 10.1007/s13238-017-0469-4
Abstract:
Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trak1 that causes hypertonia in mice. Moreover, elevated Trak1 protein expression is associated with several types of cancers and variants in Trak1 are linked to childhood absence epilepsy in humans. Despite the importance of Trak1 in health and disease, the mechanisms of Trak1 action remain unclear and the pathogenic effects of Trak1 mutation are unknown. Here we report that Trak1 has a crucial function in regulation of mitochondrial fusion. Depletion of Trak1 inhibits mitochondrial fusion, resulting in mitochondrial fragmentation, whereas overexpression of Trak1 elongates and enlarges mitochondria. Our analyses revealed that Trak1 interacts and colocalizes with mitofusins on the outer mitochondrial membrane and functions with mitofusins to promote mitochondrial tethering and fusion. Furthermore, Trak1 is required for stress-induced mitochondrial hyperfusion and pro-survival response. We found that hypertonia-associated mutation impairs Trak1 mitochondrial localization and its ability to facilitate mitochondrial tethering and fusion. Our findings uncover a novel function of Trak1 as a regulator of mitochondrial fusion and provide evidence linking dysregulated mitochondrial dynamics to hypertonia pathogenesis.
Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos
Jinzhu Xiang, Suying Cao, Liang Zhong, Hanning Wang, Yangli Pei, Qingqing Wei, Bingqiang Wen, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Genhua Yue, Bing Lim, Jianyong Han
2018, 9(8): 717-728. doi: 10.1007/s13238-017-0470-y
Abstract:
It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.
Letters
CRTC2 modulates hepatic SREBP1c cleavage by controlling Insig2a expression during fasting
Yuanyuan Zhang, Yi Liu, Liqun Chen, Yiguo Wang, Jinbo Han
2018, 9(8): 729-732. doi: 10.1007/s13238-018-0538-3
Abstract:
APEX2-tagging of Sigma 1-receptor indicates subcellular protein topology with cytosolic N-terminus and ER luminal C-terminus
Timur Mavylutov, Xi Chen, Lianwang Guo, Jay Yang
2018, 9(8): 733-737. doi: 10.1007/s13238-017-0468-5
Abstract:
Structural and biochemical insights into human zinc finger protein AEBP2 reveals interactions with RBBP4
Aiai Sun, Fudong Li, Zhonghua Liu, Yiyang Jiang, Jiahai Zhang, Jihui Wu, Yunyu Shi
2018, 9(8): 738-742. doi: 10.1007/s13238-017-0483-6
Abstract:
CD146 is essential for PDGFRβ-induced pericyte recruitment
Jianan Chen, Yongting Luo, Hongxin Huang, Shuilong Wu, Jing Feng, Jingjing Zhang, Xiyun Yan
2018, 9(8): 743-747. doi: 10.1007/s13238-017-0484-5
Abstract:

Current Issue

March, 2019

Volume 10, Issue 3

Pages 157-233

About the cover

Metastasis is the leading cause of human cancer deaths.Unfortunately, no approved drugs are available for antimetastatic treatment. In this study, high-throughputsequencing-based high-throughput screening (HTS2) anda breast cancer lung metastasis (BCLM)-associated genesignature were combined to discover anti-metastatic drugs.After screening of thousands of compounds, Shao et al.identifed Ponatinib as a BCLM inhibitor. Ponatinib signifcantlyinhibited the migration and mammosphere formation of breastcancer cells in vitro and blocked BCLM in multiple mousemodels. This study may facilitate the therapeutic treatment ofBCLM as well as other metastases.

Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang Beijing 100101, China

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