• 생명과학회지
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• 제28권2호
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• pp.265-273
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• 2018

에스트로겐(E2)은 유방암의 발달과 진행에 관여하며, 에스트로겐 수용체(ER)에 의해 매개된다. ER은 유방암세포에서 epidermal growth factor receptor와 insulin-like growth factor-1 receptor의 신호전달경로들 사이에서 다양한 cross-talk을 통하여 세포의 증식, 이주, 침습 및 약물에 대한 저항성을 일으키는데 중요한 역할을 수행한다. 유방암은 내분비신호전달의 항상성 붕괴에 의해 주로 발생되며, 특히 E2/IGF-1/EGF와 ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR, 그리고 이들의 세포내 신호전달 매개인자들의 통제되지 않는 발현과 활성증가에 의해 유발된다. 이러한 변화는 E2와 성장인자 신호전달 사이의 복잡한 cross-talk에 영향을 주어 결국 암의 진행과 내분비조절인자들에 대한 저항성을 갖게 된다. 따라서, E2와 성장인자들 사이의 cross-talk에 관한 분자적 기전을 단계별로 규명하는 것은 유방암의 다양한 유형에 따른 맞춤형 치료에 기여할 것으로 사료된다. 특히, 다양한 유전형 및 표현형을 가진 유방암의 치료를 위한 전략으로서, ER+ 호르몬의존성 유방암세포에 대한 aromatase 억제제 및 E2작용 차단제의 사용과 E2와 성장인자들 사이의 cross-talk에 의한 암세포의 증식억제를 위한 IGF-1R/EGFR 활성차단제의 사용 등을 들 수 있다. 뿐만 아니라, ER과 EGFR/IGF-1R 사이의 cross-talk에 의해 조절되는 ECM 분자들의 발현변화는 유방암세포의 전이에 대한 표적치료제를 위해 활용될 수 있다. 따라서, 암의 진행과 관련된 ER, GPER, IGF-1R 및 EGFR 매개에 의한 신호전달경로들 사이의 cross-talk에 관한 보다 더 자세한 분자적 수준의 규명이 필요할 것으로 사료된다.

• Molecules and Cells
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• 제26권2호
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• pp.107-112
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• 2008

Invasion mechanisms of pathogens and counteracting defense mechanisms of plants are highly diverse and perpetually evolving. While most classical studies of plant defense have focused only on defense-specific factor-mediated responses, recent work is beginning to shed light on the involvement of non-stress signal components, especially growth and developmental processes. This shift in focus links plant resistance more closely with growth and development. In this review, we summarize our current understanding of how pathogens manipulate host developmental processes and, conversely, of how plants deploy their developmental processes for self-protection. We conclude by introducing our recent work on UNI, a novel R protein in Arabidopsis which mediates cross-talk between developmental processes and defense responses.

• 생명과학회지
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• 제30권2호
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• pp.211-220
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• 2020

CAR의 활성은 리간드 결합 뿐만 아니라, 세포외신호전달 경로를 통한 관련 조절인자들의 인산화, 전사 조절인자들과의 상호작용, 그리고 coactivators 및 corepressors의 동원, 분해 및 발현 등에 의해 조절되며, 이러한 CAR의 활성 조절은 또한 외인성 화학물질과 에너지 대사, 세포의 증식 및 사멸을 포함한 다양한 생리적 항상성 조절에 영향을 미친다. CAR는 ERK1/2의 신호전달경로에 의해 인산화되어 Hsp-90/CCRP와 복합체를 형성하여 세포질 내에 잔류하는 반면, PB는 ERK1/2를 억제하여 downstream 신호전달 조절인자들의 탈인산화를 유발하고, 활성화된 RACK-1/PP2A를 동원하여 CAR를 탈인산화 함으로써 핵 이동 및 전사 활성을 유도한다. CAR의 활성은 FoxO1 및 PGC-1α와의 cross-talk을 통하여 각각 전사 활성 억제와 ubiquitination을 통한 단백질 분해를 유도하여 당합성과정에 관여하는 PEPCK 및 G6Pase 유전자의 발현을 억제한다. CAR에 의한 지방의 합성과 산화 조절은 각각 PPARγ 및 PPARα와의 cross-talk에 의한 PGC-1α의 분해와 CPT-1의 발현 억제 또는 PGC-1α와의 결합을 통해 지방 합성 유전자의 발현 억제와 조직 특이적 산화 억제 또는 촉진으로 이루어진다. CAR는 FoxO1의 억제를 통한 p21의 발현 억제와 cyclin D1의 발현을 유도하여 세포 증식을 촉진하는 반면, GADD45B의 발현을 통한 MKK7과 JNK1의 활성을 억제하여 세포 사멸을 억제한다. 결론적으로, CAR는 세포외신호전달 경로와 세포내 조절인자들과의 다양한 상호작용을 통하여 외인성 화학물질의 대사뿐만 아니라 에너지 대사 및 세포의 성장과 사멸의 조절을 통한 항상성 유지에 관여한다.

• BMB Reports
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• 제38권1호
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• pp.9-16
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• 2005

Transforming Growth Factor (TGF)-$\beta$ family, including TGF-$\beta$, bone morphorgenic protein (BMP), and activn, plays an important role in essential cellular functions such as proliferation, differentiation, apoptosis, tissue remodeling, angiognesis, immune responses, and cell adhesions. TGF-$\beta$ predominantly transmits the signals through serine/threonine receptor kinases and cytoplasmic proteins called Smads. Since the discovery of TGF-$\beta$ in the early 1980s, the dysregulation of TGF-$\beta$/Smad signaling has been implicated in the pathogenesis of human diseases. Among signal transducers in TGF-$\beta$/Smad signaling, inhibitory Smads (I-Smads), Smad6 and Smad7, act as major negative regulators forming autoinhibitory feedback loops and mediate the cross-talking with other signaling pathways. Expressions of I-Smads are mainly regulated on the transcriptional levels and post-translational protein degradations and their intracellular levels are tightly controlled to maintain the homeostatic balances. However, abnormal levels of I-Smads in the pathological conditions elicit the altered TGF-$\beta$ signaling in cells, eventually causing TGF-$\beta$-related human diseases. Thus, exploring the molecular mechanisms about the regulations of I-Smads may provide the therapeutic clues for human diseases induced by the abnormal TGF-$\beta$ signaling.

• Molecules and Cells
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• 제43권1호
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• pp.23-33
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• 2020

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 TP53 gene have been detected in more than half of all human cancers. While the non-canonical NF-κB and p53 pathways have been explored for several decades, no studies to date have documented potential cross-talk between these two cancer-related mechanisms. Here, we demonstrate that p53 negatively regulates NIK in an miRNA-dependent manner. Overexpression of p53 decreased the levels of NIK, leading to inhibition of the non-canonical NF-κB pathway. Conversely, its knockdown led to increased levels of NIK, IKKα phosphorylation, and p100 processing. Additionally, miR-34b induced by nutlin-3 directly targeted the coding sequences (CDS) of NIK. Treatment with anti-miR-34b-5p augmented NIK levels and subsequent non-canonical NF-κB signaling. Our collective findings support a novel cross-talk mechanism between non-canonical NF-κB and p53.

• Clinical and Experimental Pediatrics
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• 제53권12호
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• pp.979-984
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• 2010

Recent progress in neonatal medicine has enabled survival of many extremely low-birth-weight infants. Prenatal steroids, surfactants, and non-invasive ventilation have helped reduce the incidence of the classical form of bronchopulmonary dysplasia characterized by marked fibrosis and emphysema. However, a new form of bronchopulmonary dysplasia marked by arrest of alveolarization remains a complication in the postnatal course of extremely low-birth-weight infants. To better understand this challenging complication, detailed alveolarization mechanisms should be delineated. Proper alveolarization involves the temporal and spatial coordination of a number of cells, mediators, and genes. Cross-talk between the mesenchyme and the epithelium through soluble and diffusible factors are key processes of alveolarization. Lung interstitial cells derived from the mesenchyme play a crucial role in alveolarization. Peak alveolar formation coincides with intense lung interstitial cell proliferation. Myofibroblasts are essential for secondary septation, a critical process of alveolarization, and localize to the front lines of alveologenesis. The differentiation and migration of myofibroblasts are strictly controlled by various mediators and genes. Disruption of this finely controlled mechanism leads to abnormal alveolarization. Since arrest in alveolarization is a hallmark of a new form of bronchopulmonary dysplasia, knowledge regarding the role of lung interstitial cells during alveolarization and their control mechanism will enable us to find more specific therapeutic strategies for bronchopulmonary dysplasia. In this review, the role of lung interstitial cells during alveolarization and control mechanisms of their differentiation and migration will be discussed.

• Molecules and Cells
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• 제40권11호
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• pp.855-863
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• 2017

Adipose tissue plays a central role in regulating dynamic cross-talk between tissues and organs. A detailed description of molecules that are differentially expressed upon changes in adipose tissue mass is expected to increase our understanding of the molecular mechanisms that underlie obesity and related metabolic co-morbidities. Our previous studies suggest a possible link between endophilins (SH3Grb2 proteins) and changes in body weight. To explore this further, we sought to assess the distribution of endophilin A2 (EA2) in human adipose tissue and experimental animals. Human paired adipose tissue samples (subcutaneous and visceral) were collected from subjects undergoing elective abdominal surgery and abdominal liposuction. We observed elevated EA2 gene expression in the subcutaneous compared to that in the visceral human adipose tissue. EA2 gene expression negatively correlated with adiponectin and chemerin in visceral adipose tissue, and positively correlated with $TNF-{\alpha}$ in subcutaneous adipose tissue. EA2 gene expression was significantly downregulated during differentiation of preadipocytes in vitro. In conclusion, this study provides a description of EA2 distribution and emphasizes a need to study the roles of this protein during the progression of obesity.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.703-712
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• 2016

Monoclonal antibodies with specific antigens have been widely used as targeted therapy for cancer. Hep88 mAb is a monoclonal antibody which shows specific binding with anti-cancer effects against the HepG2 cell line. However, its mechanisms of action are still not completely understood. We examined cell cycling and apoptosis by flow cytometry and mRNA expression of factors involved in apoptosis and paraptosis in Hep88 mAb-treated HepG2 cells by real-time PCR. The cell-cycle analysis demonstrated that growth-inhibitory activity was associated with G2/M cell cycle arrest. Hep88 mAb induced a significant increase in apoptotic cell populations in a dose- and time-dependent manner. The mRNA expression results also suggested that the process triggered by Hep88 mAb involved up-regulation of tumor suppressor p53, pro-apoptotic Bax, Cathepsin B, Caspase-3 and Caspase-9, with a decrease of anti-apoptotic Bcl-2 - thus confirming paraptosis and apoptosis programmed cell death. These findings represent new insights into the molecular mechanisms underlying the anti-cancer properties of Hep88 mAb in liver cancer cells.

• The Korean Journal of Pain
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• 제29권1호
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• pp.3-11
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• 2016

A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration.

• 한국발생생물학회지:발생과생식
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• 제5권2호
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• pp.93-100
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• 2001

태아가 모체의 면역 거부 반응으로부터 회피될 수 있는 기전에 관한 연구는 반세기를 지내왔지만 아직까지 규명되지 못하고 있다. 태아모체간 계면에서의 면역학적 기전이상은 자연 유산 및 습관성 유산, 태아발육제한, 임신성 고혈압 질환, 보조 생식술 후 착상실패, 태아 사망 등 각종 임신 합병증들의 병인으로 작용하므로 이 기전 규명은 매우 중요하다. 본 종설에서는 현재까지 이 면역학적 기전에 관해 밝혀진 내용들이 그 중요성의 정도순으로 기술되었다. 그 기전 이해에 관해서는 1) 융모외 세포영양모세포(extravillous cytotrophoblasts)가 표현하는 인백혈구 항원(HLA-C, E, G)과 자연살세포 수용체(NK cell receptor)들과 상호 관계가 그 핵심으로 2) 면역 조정(immunomodulation)과 3) 선천면역(innate immunity)이 주된 기전이고 4) 보체(complement) 등 인백혈구 항원계(HLA system)이외의 인자들이 관여함 등으로 요약될 수 있고 이러한 무수한 기전들의 종합적인 면역 조정 결과가 해당 임신의 예후를 결정하게 될 것이다. 향후, 각 기전에 대한 연구들, 특히 융모외 세포영양모세포(extravillous cytotrophoblasts)의 인백혈구 항원(HLA antigens)과 그 수용체(receptor)들의 조절기전, 사이토카인(cytokine), 보체(complement) 등의 역할에 관한 더욱 많은 연구가 진척되어야할 것이다.