Editorial

It is a pleasure to organize this special issue of Molecular Plant on Epigenetics and Plant Development. There has been a groundswell of support for this special issue, with papers having been submitted from most of the colleagues we invited. In this issue, there are 16 research articles and reviews. More articles on topics related to the special issue will appear in the next issue. Note that this issue of the journal also includes six regular submissions on topics not related to epigenetics and development, which reflects our commitment to publish all high-quality articles on a timely basis.     

SHANK2 is a frequently amplified oncogene with evolutionarily conserved roles in regulating Hippo signaling

Dysfunction of the Hippo pathway enables cells to evade contact inhibition and provides advantages for cancerous overgrowth.However,for a significant portion of human cancer,how Hippo signaling is perturbed remains unknown.To answer this question,we performed a genome-wide screening for genes that affect the Hippo pathway in Drosophila and cross-referenced the hit genes with human cancer genome.In our screen,Prosap was identified as a novel regulator of the Hippo pathway that potently affects tissue growth.Interestingly,a mammalian homolog of Prosap,SHANK2,is the most frequently amplified gene on 11 q13,a major tumor amplicon in human cancer.Gene amplification profile in this 11q13 amplicon clearly indicates selective pressure for SHANK2 amplification.More importantly,across the human cancer genome,SHANK2 is the most frequently amplified gene that is not located within the Myc amplicon.Further studies in multiple human cell lines confirmed that SHANK2 overexpression causes deregulation of Hippo signaling through competitive binding for a LATS1 activator,and as a potential oncogene,SHANK2 promotes cellular transformation and tumor formation in vivo.In cancer cell lines with deregulated Hippo pathway,depletion of SHANK2 restores Hippo signaling and ceases cellular proliferation.Taken together,these results suggest that SHANK2 is an evolutionarily conserved Hippo pathway regulator,commonly amplified in human cancer and potently promotes cancer.Our study for the first time illustrated oncogenic function of SHANK2,one of the most frequently amplified gene in human cancer.Furthermore,given that in normal adult tissues,SHANK2 s expression is largely restricted to the nervous system,SHANK2 may represent an interesting target for anticancer therapy.     

GSK-3β as a driving force in ovarian cancer

Ovarian cancer is one of the most lethal malignancies in women. Identification of new therapeutic targets would provide opportunities for developing potentially more effective treatment regimes. In the July issue of Cell Research, Cao et al. reports that glycogen synthase kinase-3β （GSK-3β） plays an important role in positively regulating the proliferation of human ovarian cancer cells, and thus it may represent such a target [ 1 ]. GSK-3β is a serine/threonine kinase that is known to be involved in regulation of β-catenin signaling, where it participates in the formation of a multi-component destruction complex that promotes the phosphorylation and subsequent degradation of β-catenin. Given that overactive β-catenin signaling is involved in many forms of human cancer, this classic mode of GSK-3β action should qualify it as a ＂tumor suppressor＂. Intriguingly, however, two recent studies have implicated that GSK-3β may actually play a pro-tumor role in pancreatic and colorectal cancers [2, 3]. Since ovarian tumors often exhibit increased expression of GSK-3β, these recent findings prompted Cao et al. to examine the potential role of GSK-3β in ovarian cancer cells.     

Excited States and Free Radicals in Biology and Medicine——Contributions from Flash Photolysis and Pulse Radiolysis

Excited states and free radicals are involved in the normal physiology of living systems; in pathological processes including lipid peroxidation, inflammation, Parkinson's disease, cancer, and ageing; in the mechanism of action of drugs, such as quinone antitumour agents, and in photochemotherapies such as the PUVA therapy of skin diseases and PDT of cancer. The chief aim of this text is to introduce the reader to this rapidly expanding field, which lies at the borderlines of physics, chemistry, biology, pharmacology, and medicine, and, in particular, to explore how time—resolved spectroscopic methods have found solutions at the molecular level to biological and medical problems.     

Mechanism of immunomodulatory drugs＇ action in the treatment of multiple myeloma

Although immunomodulatory drugs （IMiDs）, such as thal- idomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma （MM）, the molecular mechanism of IMiDs＇ action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflam- matory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs＇ target protein, IMiDs＇ target protein＇s functional role, and the potential molecular mechanisms of IMiDs resistance will be discussed. We wish, by presentation of our naive discussion, that this review article will facilitate further investigation in these fields.     

TRAF4 mediates activation of TGF-β signaling and is a biomarker for oncogenesis in breast cancer

The tumor-promoting arm of transforming growth factor beta(TGF-β)receptor signaling contributes to advanced cancer progression and is considered a master regulator of breast cancer metastasis.In mammals,there are six distinct members in the tumor-necrosis factor receptor(TNFR)-associated factor(TRAF)family(TRAF1–TRAF6),with the function of TRAF4 not being extensively studied in the past decade.Although numerous studies have suggested that there is elevated TRAF4 expression in human cancer,it is still unknown in which oncogenic pathway TRAF4 is mainly implicated.This review highlights TGF-β-induced SMAD-dependent signaling and non-SMAD signaling as the major pathways regulated by TRAF4 involved in breast cancer metastasis.     

Forthcoming Special lssue on Calcium Signaling!!

A special issue on“Calcium Signaling”will be published in July issue of Acta Pharmacologica.Sinica.From the following selected articles you will see that the approach we take is to give a broad picture on recent developments in the field of calcium signalling in various cells,tissues,and systems.     

Selective degradation of the IκB kinase （IKK） by autophagy

Proteasome-mediated degradation and autophagy are the two major pathways mediating the turnover of cellular proteins. The proteasomal pathway is known to be a highly specific and regulated process mediating the degradation of short-lived proteins such as many important factors involved in cellular signaling. In contrast, it is generally thought that autophagy is rather nonselective as it is responsible for the bulk degradation of long-lived proteins and organelles. Challenging this general view, in this issue of Cell Research, Qing et al. report that selective degradation of the IκB kinase （IKK） triggered by the loss of Hsp90 function is mediated by autophagy [1].     

Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer

Glycosylation is a common posttranslational modification on membrane-associated and secreted proteins that is of pivotal importance for regulating cell functions.Aberrant glycosylation can lead to uncontrolled cell proliferation,cell-matrix interactions,migration and differentiation,and has been shown to be involved in cancer and other diseases.The epithelial-to-mesenchymal transition is a key step in the metastatic process by which cancer cells gain the ability to invade tissues and extravasate into the bloodstream.This cellular transformation process,which is associated by morphological change,loss of epithelial traits and gain of mesenchymal markers,is triggered by the secreted cytokine transforming growth factor-β(TGF-β).TGF-βbioactivity is carefully regulated,and its effects on cells are mediated by its receptors on the cell surface.In this review,we first provide a brief overview of major types of glycans,namely,N-glycans,O-glycans,glycosphingolipids and glycosaminoglycans that are involved in cancer progression.Thereafter,we summarize studies on how the glycosylation of TGF-βsignaling components regulates TGF-βsecretion,bioavailability and TGF-βreceptor function.Then,we review glycosylation changes associated with TGF-β-induced epithelial-to-mesenchymal transition in cancer.Identifying and understanding the mechanisms by which glycosylation affects TGF-βsignaling and downstream biological responses will facilitate the identification of glycans as biomarkers and enable novel therapeutic approaches.     

Special Issue on ＂Metagenomics of Marine Environments＂

We are pleased to announce a special issue on ＂Metagenomics of Marine Environments＂ of the journal Genomics, Proteomics ＆ Bioinformatics （GPB）, aiming to provide a platform for high-quality papers focusing on the topic and we invite submissions for this special issue （to be published in August of 2015）.
With most microbes being difficult or impossible to culture, metagenomic approaches based on culture- independent genomic sequencing provide the first real insight of the magnitude and diversity of microbial life that remains largely uncharted. The first metagenomic study of surface water of the Sargasso Sea revealed roughly 1800 species of microbes found in these samples, with 150 new bacterial species and over 1.2 million new genes. The astounding number of genes found in these samples suggests that microbial life in the ocean is far more abundant and diverse than one would expect.     

Special Issue on ‘‘Genome Stability'

正We are very pleased to announce a special issue,to be published in June,2016,on‘‘Genome Stability’’in the journal Genomics,ProteomicsBioinformatics(GPB).This special issue aims to provide a platform for specialists or experts in the field to report their results and share their opinions on the topic.We are inviting you to submit high-quality papers to this special issue.The guest editors for this special issue are Dr.Zhao-Qi Wang     

Advances in cellular technology in the hematology field: What have we learned so far?

Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-theart concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research.     

Dysregulated lipid metabolism in cancer

Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.