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  • MinireviewSeptember 30, 2020

    0 699 1195

    Classifying the Linkage between Adipose Tissue Inflammation and Tumor Growth through Cancer-Associated Adipocytes

    Yae Chan Song , Seung Eon Lee , Young Jin , Hyun Woo Park , Kyung-Hee Chun , and Han-Woong Lee

    Mol. Cells 2020; 43(9): 763-773 https://doi.org/10.14348/molcells.2020.0118
    Abstract

    Abstract : Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

  • MinireviewSeptember 30, 2020

    0 1013 1620

    WNT Signaling in Lung Repair and Regeneration

    Ahmed A. Raslan and Jeong Kyo Yoon

    Mol. Cells 2020; 43(9): 774-783 https://doi.org/10.14348/molcells.2020.0059
    Abstract

    Abstract : The lung has a vital function in gas exchange between the blood and the external atmosphere. It also has a critical role in the immune defense against external pathogens and environmental factors. While the lung is classified as a relatively quiescent organ with little homeostatic turnover, it shows robust regenerative capacity in response to injury, mediated by the resident stem/progenitor cells. During regeneration, regionally distinct epithelial cell populations with specific functions are generated from several different types of stem/progenitor cells localized within four histologically distinguished regions: trachea, bronchi, bronchioles, and alveoli. WNT signaling is one of the key signaling pathways involved in regulating many types of stem/progenitor cells in various organs. In addition to its developmental role in the embryonic and fetal lung, WNT signaling is critical for lung homeostasis and regeneration. In this minireview, we summarize and discuss recent advances in the understanding of the role of WNT signaling in lung regeneration with an emphasis on stem/progenitor cells.

  • Research ArticleSeptember 30, 2020

    0 406 465

    Insight into Structural Aspects of Histidine 284 of Daphnia magna Arginine Kinase

    Zhili Rao , So Young Kim , Xiaotong Li , Da Som Kim , Yong Ju Kim , and Jung Hee Park

    Mol. Cells 2020; 43(9): 784-792 https://doi.org/10.14348/molcells.2020.0136
    Abstract

    Abstract : Arginine kinase (AK), a bioenergy-related enzyme, is distributed widely in invertebrates. The role of highly conserved histidines in AKs is still unascertained. In this study, the highly conserved histidine 284 (H284) in AK of Daphnia magna (DmAK) was replaced with alanine to elucidate the role of H284. We examined the alteration of catalytic activity and structural changes of H284A in DmAK. The catalytic activity of H284A was reduced dramatically compared to that in wild type (WT). Thus the crystal structure of H284A displayed several structural changes, including the alteration of D324, a hydrogen-bonding network around H284, and the disruption of π-stacking between the imidazole group of the H284 residue and the adenine ring of ATP. These findings suggest that such alterations might affect a conformational change of the specific loop consisting of G310-V322 at the antiparallel β-sheet region. Thus, we speculated that the H284 residue might play an important role in the conformational change of the specific loop when ATP binds to the substrate-binding site of DmAK.

  • Research ArticleSeptember 30, 2020

    0 372 503

    MicroRNA 449c Mediates the Generation of Monocytic Myeloid-Derived Suppressor Cells by Targeting STAT6

    Xiaoqing Han , Tao Luan , Yingying Sun , Wenyi Yan , Dake Wang , and Xianlu Zeng

    Mol. Cells 2020; 43(9): 793-803 https://doi.org/10.14348/molcells.2020.2307
    Abstract

    Abstract : Myeloid-derived suppressor cells (MDSCs) promote tumour progression by contributing to angiogenesis, immunosuppression, and immunotherapy resistance. Although recent studies have shown that microRNAs (miRNAs) can promote the expansion of MDSCs in the tumour environment, the mechanisms involved in this process are largely unknown. Here, we report that microRNA 449c (miR-449c) expression was upregulated in myeloid progenitor cells upon activation of C-X-C motif chemokine receptor 2 (CXCR2) under tumour conditions. MiR-449c upregulation increased the generation of monocytic MDSCs (mo-MDSCs). The increased expression of miR-449c could target STAT6 mRNA in myeloid progenitor cells to shift the differentiation balance of myeloid progenitor cells and lead to an enhancement of the mo-MDSCs population in the tumour environment. Thus, our results demonstrate that the miR-449c/STAT6 axis is involved in the expansion of mo-MDSCs from myeloid progenitor cells upon activation of CXCR2, and thus, inhibition of miR-449c/STAT6 signalling may help to attenuate tumour progression.

  • Research ArticleSeptember 30, 2020

    0 378 290

    EMPAS: Electron Microscopy Screening for Endogenous Protein Architectures

    Gijeong Kim , Seongmin Jang , Eunhye Lee , and Ji-Joon Song

    Mol. Cells 2020; 43(9): 804-812 https://doi.org/10.14348/molcells.2020.0163
    Abstract

    Abstract : In cells, proteins form macromolecular complexes to execute their own unique roles in biological processes. Conventional structural biology methods adopt a bottom-up approach starting from defined sets of proteins to investigate the structures and interactions of protein complexes. However, this approach does not reflect the diverse and complex landscape of endogenous molecular architectures. Here, we introduce a top-down approach called Electron Microscopy screening for endogenous Protein ArchitectureS (EMPAS) to investigate the diverse and complex landscape of endogenous macromolecular architectures in an unbiased manner. By applying EMPAS, we discovered a spiral architecture and identified it as AdhE. Furthermore, we performed screening to examine endogenous molecular architectures of human embryonic stem cells (hESCs), mouse brains, cyanobacteria and plant leaves, revealing their diverse repertoires of molecular architectures. This study suggests that EMPAS may serve as a tool to investigate the molecular architectures of endogenous macromolecular proteins.

  • Research ArticleSeptember 30, 2020

    0 408 562

    Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species

    Yeung-Chul Mun , Jee Young Ahn , Eun Sun Yoo , Kyoung Eun Lee , Eun Mi Nam , Jungwon Huh , Hyun Ae Woo , Sue Goo Rhee , and Chu Myong Seong

    Mol. Cells 2020; 43(9): 813-820 https://doi.org/10.14348/molcells.2020.2234
    Abstract

    Abstract : NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2’, 7’-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOXTM Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO2 (Cysteine sulfinic acid, Cys–SO2H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO2 form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.

  • Research ArticleSeptember 30, 2020

    0 417 525

    C9orf72-Associated Arginine-Rich Dipeptide Repeat Proteins Reduce the Number of Golgi Outposts and Dendritic Branches in Drosophila Neurons

    Jeong Hyang Park , Chang Geon Chung , Jinsoo Seo , Byung-Hoon Lee , Young-Sam Lee , Jung Hyun Kweon , and Sung Bae Lee

    Mol. Cells 2020; 43(9): 821-830 https://doi.org/10.14348/molcells.2020.0130
    Abstract

    Abstract : Altered dendritic morphology is frequently observed in various neurological disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the cellular and molecular basis underlying these pathogenic dendritic abnormalities remains largely unclear. In this study, we investigated dendritic morphological defects caused by dipeptide repeat protein (DPR) toxicity associated with G4C2 expansion mutation of C9orf72 (the leading genetic cause of ALS and FTD) in Drosophila neurons and characterized the underlying pathogenic mechanisms. Among the five DPRs produced by repeat-associated non-ATG translation of G4C2 repeats, we found that arginine-rich DPRs (PR and GR) led to the most significant reduction in dendritic branches and plasma membrane (PM) supply in Class IV dendritic arborization (C4 da) neurons. Furthermore, expression of PR and GR reduced the number of Golgi outposts (GOPs) in dendrites. In Drosophila brains, expression of PR, but not GR, led to a significant reduction in the mRNA level of CrebA, a transcription factor regulating the formation of GOPs. Overexpressing CrebA in PR-expressing C4 da neurons mitigated PM supply defects and restored the number of GOPs, but the number of dendritic branches remained unchanged, suggesting that other molecules besides CrebA may be involved in dendritic branching. Taken together, our results provide valuable insight into the understanding of dendritic pathology associated with C9-ALS/FTD.

  • Research ArticleSeptember 30, 2020

    0 345 375

    Crystal Structure of β-Carbonic Anhydrase CafA from the Fungal Pathogen Aspergillus fumigatus

    Subin Kim , Jungyoon Yeon , Jongmin Sung , and Mi Sun Jin *

    Mol. Cells 2020; 43(9): 831-840 https://doi.org/10.14348/molcells.2020.0168
    Abstract

    Abstract : The β-class of carbonic anhydrases (β-CAs) are zinc metalloenzymes widely distributed in the fungal kingdom that play essential roles in growth, survival, differentiation, and virulence by catalyzing the reversible interconversion of carbon dioxide (CO2) and bicarbonate (HCO3). Herein, we report the biochemical and crystallographic characterization of the β-CA CafA from the fungal pathogen Aspergillus fumigatus, the main causative agent of invasive aspergillosis. CafA exhibited apparent in vitro CO2 hydration activity in neutral to weak alkaline conditions, but little activity at acidic pH. The high-resolution crystal structure of CafA revealed a tetramer comprising a dimer of dimers, in which the catalytic zinc ion is tetrahedrally coordinated by three conserved residues (C119, H175, C178) and an acetate anion presumably acquired from the crystallization solution, indicating a freely accessible ″open″ conformation. Furthermore, knowledge of the structure of CafA in complex with the potent inhibitor acetazolamide, together with its functional intolerance of nitrate (NO3) ions, could be exploited to develop new antifungal agents for the treatment of invasive aspergillosis.

Mol. Cells
Sep 30, 2022 Vol.45 No.9
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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