Hirota Fujiki, Tatsuro Watanabe, Eisaburo Sueoka, Anchalee Rawangkan, and Masami SuganumaMol. Cells 2018; 41(2): 73-82 https://doi.org/10.14348/molcells.2018.2227
Abstract : Cancer preventive activities of green tea and its main constituent, (?)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as green tea extract and underlying molecular mechanisms. The first part of this review summarizes ground-breaking topics with EGCG and green tea extract: 1) Delayed cancer onset as revealed by a 10-year prospective cohort study, 2) Prevention of colorectal adenoma recurrence by a double-blind randomized clinical phase II trial, 3) Inhibition of metastasis of B16 melanoma cells to the lungs of mice, 4) Increase in the average value of Young’s moduli, i.e., cell stiffness, for human lung cancer cell lines and inhibition of cell motility and 5) Synergistic enhancement of anticancer activity against human cancer cell lines with the combination of EGCG and anticancer compounds. In the second part, we became interested in cancer stem cells (CSCs). 1) Cancer stem cells in mouse skin carcinogenesis by way of introduction, after which we discuss two subjects from our review on human CSCs reported by other investigators gathered from a search of PubMed, 2) Expression of stemness markers of human CSCs compared with their parental cells, and 3) EGCG decreases or increases the expression of mRNA and protein in human CSCs. On this point, EGCG inhibited self-renewal and expression of pluripotency-maintaining transcription factors in human CSCs. Human CSCs are thus a target for cancer prevention and treatment with EGCG and green tea catechins.
Jae Hyung Park, Ji Eun Shin, and Hyun Woo ParkMol. Cells 2018; 41(2): 83-92 https://doi.org/10.14348/molcells.2018.2242
Abstract : The biological significance and deregulation of the Hippo pathway during organ growth and tumorigenesis have received a surge of interest in the past decade. The Hippo pathway core kinases, MST1/2 and LATS1/2, are tumor suppressors that inhibit the oncogenic nuclear function of YAP/TAZ and TEAD. In addition to earlier studies that highlight the role of Hippo pathway in organ size control, cell proliferation, and tumor development, recent evidence demonstrates its critical role in cancer stem cell biology, including EMT, drug resistance, and self-renewal. Here we provide a brief overview of the regulatory mechanisms of the Hippo pathway, its role in cancer stem cell biology, and promising therapeutic interventions.
Sooeun Oh, Minkoo Seo, Jun-Sub Choi, Choun-Ki Joo, and Suk Kyeong LeeMol. Cells 2018; 41(2): 93-102 https://doi.org/10.14348/molcells.2018.2163
Abstract : Discoidin domain receptor 1 (DDR1) is involved in tumorigenesis and angiogenesis. However, its role in lymphangiogenesis has been unknown. Here, we tested whether downregulation of DDR1 expression by miR-199a/b can suppress lymphangiogenesis. We also aimed to identify miRNA target site(s) in the 3′ untranslated region (UTR) of
Byeonggyu Park, Dong-Yeop Shin, and Taeck Joong JeonMol. Cells 2018; 41(2): 103-109 https://doi.org/10.14348/molcells.2018.2170
Abstract : Calcium ions are involved in the regulation of diverse cellular processes. Fourteen genes encoding calcium binding proteins have been identified in
Junwon Lee, Sang-Hwi Choi, Dongjin R Lee, Dae-Sung Kim, and Dong-Wook KimMol. Cells 2018; 41(2): 110-118 https://doi.org/10.14348/molcells.2018.2210
Abstract : The objective of this study was to induce the production of isthmic organizer (IsO)-like cells capable of secreting fibroblast growth factor (FGF) 8 and WNT1 from human embryonic stem cells (ESCs). The precise modulation of canonical Wnt signaling was achieved in the presence of the small molecule CHIR99021 (0.6 μM) during the neural induction of human ESCs, resulting in the differentiation of these cells into IsO-like cells having a midbrain-hindbrain border (MHB) fate in a manner that recapitulated their developmental course
Ying Zhu, Hao-liang Zhang, Qi-ying Wang, Min-jing Chen, and Lin-bo LiuMol. Cells 2018; 41(2): 119-126 https://doi.org/10.14348/molcells.2018.2235
Abstract : microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells.
Sunwoo Min, Yong Won Choi, Hansol Yun, Sujin Jo, Jae-Hoon Ji, and Hyeseong ChoMol. Cells 2018; 41(2): 127-133 https://doi.org/10.14348/molcells.2018.2244
Abstract : Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.
Yerim Lee, Charny Park, Sanghyuk Lee, Daekee Lee, and Jaesang KimMol. Cells 2018; 41(2): 134-139 https://doi.org/10.14348/molcells.2018.2246
Abstract : Here, we report isolation of multiple long non-coding RNAs (lncRNAs) expressed tissue-specifically during murine embryogenesis. One of these, subsequently came to be known as
Allen Eugene Hong, Min Sook Ryu, Seung Jun Kim, Seung Yong Hwang, and In Kyoung LimMol. Cells 2018; 41(2): 140-149 https://doi.org/10.14348/molcells.2018.2257
Abstract : The TIS21/BTG2/PC3 gene belongs to the antiproliferative gene (APRO) family and exhibits tumor suppressive activity. However, here we report that TIS21 controls lipid metabolism, rather than cell proliferation, under fasting condition. Using microarray analysis, whole gene expression changes were investigated in liver of TIS21 knockout (TIS21-KO) mice after 20 h fasting and compared with wild type (WT). Peroxisome proliferator-activated receptor alpha (PPARα) target gene expression was almost absent in contrast to increased lipid synthesis in the TIS21-KO mice compared to WT mice. Immunohistochemistry with hematoxylin and eosin staining revealed that lipid deposition was focal in the TIS21-KO liver as opposed to the diffuse and homogeneous pattern in the WT liver after 24 h starvation. In addition, cathepsin E expression was over 10 times higher in the TIS21-KO liver than that in the WT, as opposed to the significant reduction of thioltransferase in both adult and fetal livers. At present, we cannot account for the role of cathepsin E. However, downregulation of glutaredoxin 2 thioltransferase expression might affect hypoxic damage in the TIS21-KO liver. We suggest that the TIS21/BTG2 gene might be essential to maintain energy metabolism and reducing power in the liver under fasting condition.
Kate E. Yu, Do-Hyoung Kim, Yong-In Kim, Walton D. Jones, and J. Eugene LeeMol. Cells 2018; 41(2): 150-159 https://doi.org/10.14348/molcells.2018.2305
Abstract : Animals use their odorant receptors to receive chemical information from the environment. Insect odorant receptors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein?protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein?protein interactions. Using this platform, we obtained the first Orco interactome from