Dohun Kim, You-Soub Lee, Duk-Hwan Kim, and Suk-Chul BaeMol. Cells 2020; 43(1): 1-9 https://doi.org/10.14348/molcells.2020.2246
Abstract : The first step in treating lung cancer is to establish the stage of the disease, which in turn determines the treatment options and prognosis of the patient. Many factors are involved in lung cancer staging, but all involve anatomical information. However, new approaches, mainly those based on the molecular biology of cancer, have recently changed the paradigm for lung cancer treatment and have not yet been incorporated into staging. In a group of patients of the same stage who receive the same treatment, some may experience unexpected recurrence or metastasis, largely because current staging methods do not reflect the findings of molecular biological studies. In this review, we provide a brief summary of the latest research on lung cancer staging and the molecular events associated with carcinogenesis. We hope that this paper will serve as a bridge between clinicians and basic researchers and aid in our understanding of lung cancer.
Dong-Hyung Cho, Jin Kyung Kim, and Eun-Kyeong JoMol. Cells 2020; 43(1): 10-22 https://doi.org/10.14348/molcells.2020.2329
Abstract : Mitochondria have several quality control mechanisms by which they maintain cellular homeostasis and ensure that the molecular machinery is protected from stress. Mitophagy, selective autophagy of mitochondria, promotes mitochondrial quality control by inducing clearance of damaged mitochondria via the autophagic machinery. Accumulating evidence suggests that mitophagy is modulated by various microbial components in an attempt to affect the innate immune response to infection. In addition, mitophagy plays a key role in the regulation of inflammatory signaling, and mitochondrial danger signals such as mitochondrial DNA translocated into the cytosol can lead to exaggerated inflammatory responses. In this review, we present current knowledge on the functional aspects of mitophagy and its crosstalk with innate immune signaling during infection. A deeper understanding of the role of mitophagy could facilitate the development of more effective therapeutic strategies against various infections.
Hanbit Jang, Seulki Park, Jaehoon Kim, Jong Hwan Kim, Seon-Young Kim, Sayeon Cho, Sung Goo Park, Byoung Chul Park, Sunhong Kim, and Jeong-Hoon KimMol. Cells 2020; 43(1): 23-33 https://doi.org/10.14348/molcells.2019.0239
Abstract : NF-κB signaling through both canonical and non-canonical pathways plays a central role in immune responses and inflammation. NF-κB?inducing kinase (NIK) stabilization is a key step in activation of the non-canonical pathway and its dysregulation implicated in various hematologic malignancies. The tumor suppressor, p53, is an established cellular gatekeeper of proliferation. Abnormalities of the
Kabsun Kim, Jung Ha Kim, Inyoung Kim, Semun Seong, and Nacksung KimMol. Cells 2020; 43(1): 34-47 https://doi.org/10.14348/molcells.2019.0232
Abstract : The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Rev-erbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Rev-erbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation
Sunghoon Jang, Fantao Kong, Jihyeon Lee, Bae Young Choi, Pengfei Wang, Peng Gao, Takashi Yamano, Hideya Fukuzawa, Byung-Ho Kang, and Youngsook LeeMol. Cells 2020; 43(1): 48-57 https://doi.org/10.14348/molcells.2019.0262
Abstract : The microalga
Hyo-Eun Son, Hyeon-Young Min, Eun-Jung Kim, and Won-Gu JangMol. Cells 2020; 43(1): 58-65 https://doi.org/10.14348/molcells.2019.0136
Abstract : Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism. Expression of osteogenic and endoplasmic reticulum (ER) stress markers were characterized by reverse-transcriptase polymerase chain reaction and western blotting. Alkaline phosphatase (ALP) staining was performed to assess ALP activity. BMP2 treatment increased mRNA expression of osteogenic genes and FTO. Overexpression of FTO increased expression of the osteogenic genes distal-less homeobox5 (Dlx5) and runt-related transcription factor 2 (Runx2). Activation of adenosine monophosphate-activated protein kinase (AMPK) increased FTO expression, and there was a positive feedback loop between FTO and p-AMPK. p-AMPK and FTO induced mild ER stress; however, tunicamycin-induced severe ER stress suppressed FTO expression and AMPK activation. In summary, FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK. FTO expression and AMPK activation induce mild ER stress. By contrast, severe ER stress inhibits osteogenic differentiation by suppressing FTO expression and AMPK activation.
Luong Dai Ly, Dat Da Ly, Nhung Thi Nguyen, Ji-Hee Kim, Heesuk Yoo, Jongkyeong Chung, Myung-Shik Lee, Seung-Kuy Cha, and Kyu-Sang ParkMol. Cells 2020; 43(1): 66-75 https://doi.org/10.14348/molcells.2019.0223
Abstract : Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca2+ depletion followed by notable store-operated Ca2+ entry. Subsequent elevation of cytosolic Ca2+ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca2+ uniporter (MCU) is the major route for Ca2+ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca2+ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca2+ concentration ([Ca2+]
Jangham Jung, Issac Choi, Hyunju Ro, Tae-Lin Huh, Joonho Choe, and Myungchull RheeMol. Cells 2020; 43(1): 76-85 https://doi.org/10.14348/molcells.2019.0210
Abstract : MARCH5 is a RING finger E3 ligase involved in mitochondrial integrity, cellular protein homeostasis, and the regulation of mitochondrial fusion and fission. To determine the function of MARCH5 during development, we assessed transcript expression in zebrafish embryos. We found that
HyeJin Lee, Jungeun Kim, Jessica A. Weber, Oksung Chung, Yun Sung Cho, Sungwoong Jho, JeHoon Jun, Hak-Min Kim, Jeongheui Lim, Jae-Pil Choi, Sungwon Jeon, Asta Blazyte, Jeremy S. Edwards, Woon Kee Paek, and Jong BhakMol. Cells 2020; 43(1): 86-95 https://doi.org/10.14348/molcells.2019.0190
Abstract : The red-crowned crane (