Article
Cell Biology
Chenqiang Jia, Zhuqing Zhang, Jun Tang, Mei-Chun Cai, Jingyu Zang, Kaixuan Shi, Yunheng Sun, Jie Wu, Hailei Shi, Weiping Shi, Pengfei Ma, Xiaojing Zhao, Zhuang Yu, Yujie Fu, Guanglei Zhuang
Summary: EMT gene signatures are positively correlated with GSDME levels in human cancers, and EMT plays a causal role in the reversible upregulation of GSDME. Core EMT-activating transcription factors ZEB1/2 directly drive the transcriptional activation of GSDME. Elevated GSDME in mesenchymally transdifferentiated derivatives can induce pyroptotic cell death and cytokine release upon exposure to antineoplastic drugs, suggesting therapeutic potential for mesenchymal malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
William W. Du, Javeria Qadir, Kevin Y. Du, Yu Chen, Nan Wu, Burton B. Yang
Summary: Current studies have shown that nuclear actin plays a significant role in the regulation of epithelial-mesenchymal transition (EMT). Different binding partners for nuclear F-actin and G-actin have been discovered, which respectively modulate EMT-promoting and EMT-repressing transcriptional events. Mechanistically, nuclear F-actin enhances the expression and stability of proteins involved in EMT promotion, while nuclear G-actin increases the expression and stability of proteins involved in EMT repression. The association between nuclear actin and EMT suggests that targeting nuclear actin dynamics for dysregulated EMT is a promising area for further study.
Review
Biochemistry & Molecular Biology
Eunjeong Kang, Jihye Seo, Haelim Yoon, Sayeon Cho
Summary: Epithelial-mesenchymal transition (EMT) plays a key role in both normal development and pathology, regulated by EMT-inducing transcription factors (EMT-TFs) to control the up- and down-regulation of specific proteins. This process is crucial for cancer metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Kai-Ting Chuang, Shyh-Shin Chiou, Shih-Hsien Hsu
Summary: This study discusses the potential of targeting transcription factors (TFs) for cancer therapy and provides a classification of various types of TFs involved in the epithelial-mesenchymal transition (EMT) process based on their DNA-binding domain (DBD) structure. It also highlights some main TFs that could be biomarkers or targeted therapies. Various strategies for targeting TFs and examples of drugs in clinical trials are listed, providing insights into TFs' role in EMT and targeted therapies.
Article
Biochemistry & Molecular Biology
Supannika Sorin, Sho Kubota, Sofiane Hamidi, Takako Yokomizo-Nakano, Kulthida Vaeteewoottacharn, Sopit Wongkham, Sakda Waraasawapati, Chawalit Pairojkul, Jie Bai, Mariko Morii, Guojun Sheng, Kanlayanee Sawanyawisuth, Goro Sashida
Summary: This study found that the high expression of high mobility group nucleosome-binding protein 3 (HMGN3) is correlated with the metastasis of cholangiocarcinoma (CCA). HMGN3 inhibits the expression of epithelial regulator genes by binding with the transcription factor SNAI2 and regulating histone deacetylases (HDACs), thereby affecting the migration capacity of CCA cells.
Review
Biochemistry & Molecular Biology
Melodie Migault, Sunil Sapkota, Cameron P. Bracken
Summary: This review discusses the large number of regulators involved in epithelial-mesenchymal transition (EMT) and the implications for understanding EMT and the genetic machinery controlling complex biological processes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Oncology
Meina Jiang, Shuai Fang, Xiaodong Zhao, Chengwei Zhou, Zhaohui Gong
Summary: EMT plays a crucial role in cancer development, especially in lung carcinoma. CircRNAs are involved in EMT-related cell invasion and metastasis, and may become promising biomarkers and therapeutic targets in cancer management.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Oncology
Hui-Jing Xu, Jing Bai, Ye Tian, Xiao Feng, Ai-Ping Chen, Jie Wang, Jin Wu, Xu-Ru Jin, Feng Zhang, Mei-Yu Quan, Chengshui Chen, Kwang-youl Lee, Jin-San Zhang
Summary: The epithelium-specific ETS transcription factor 1 (ESE1) has been found to be upregulated in primary pancreatic ductal adenocarcinoma (PDAC). Interestingly, high expression of ESE1 is associated with better relapse-free survival in PDAC patients. ESE1 exhibits dual roles in regulating malignant properties of PDAC cells by promoting cell proliferation when overexpressed and enhancing epithelial-mesenchymal transition (EMT) phenotype when downregulated. ESE1 interacts with TGF-beta signaling to modulate EMT phenotype in PDAC.
Review
Chemistry, Medicinal
Jihye Seo, Jain Ha, Eunjeong Kang, Sayeon Cho
Summary: The complex orchestration of gene expression during the transition of epithelial cells into mesenchymal cells is crucial in cancer development and metastasis. EMT-TFs, as primary regulators of this process, play key roles in metastasis and have been implicated in cancer therapy resistance. This review focuses on three main EMT-TFs - Snail, Twist1, and ZEB1 - and their relationship to drug resistance, as well as possible future approaches targeting EMT-TFs.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Review
Oncology
Zihang Ling, Bin Cheng, Xiaoan Tao
Summary: Oral squamous cell carcinoma (OSCC) is the most common malignancy in global oral cancer, with a low survival rate due to tumor metastasis and recurrence. Epithelial-to-mesenchymal transition (EMT) plays a key role in tumor metastasis and has attracted significant attention. Further research on the role of EMT in OSCC may provide novel insights for developing strategies to combat this type of cancer.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Biochemical Research Methods
Yingying Ma, Songbiao Zhu, Meiqi Yi, Wenhao Zhang, Yuanyuan Xue, Xiaohui Liu, Haiteng Deng
Summary: Protein S-glutathionylation is an important post-translational modification that regulates cellular processes. This study investigated the changes in glutathionylome during epithelial-mesenchymal transition (EMT) and found that the glutathionylation level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) increased, inhibiting its enzymatic activity and promoting EMT.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Multidisciplinary Sciences
Michela Serresi, Sonia Kertalli, Lifei Li, Matthias Jurgen Schmitt, Yuliia Dramaretska, Jikke Wierikx, Danielle Hulsman, Gaetano Gargiulo
Summary: Research has shown that chromatin regulators have a broader impact on EMT interconversion in lung cancer cells than kinases, and the loss of ARID1A, DOT1L, BRD2, and ZMYND8 may have nondeterministic and sometimes opposite consequences. These findings reveal general principles underlying transcriptional control of cancer cell plasticity.
Article
Oncology
Yuxiang Liu, Taolin Chen, Mingyue Guo, Yu Li, Qian Zhang, Guixiang Tan, Li Yu, Yongjun Tan
Summary: FOXP2, a language-related gene, interacts with FOXA2 in breast cancer cells to inhibit EMT by activating the transcription of certain genes like E-cadherin and PHF2. The results suggest a collaborative role of FOXP2 and FOXA2 in regulating EMT in breast cancer cells.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Paula I. Escalante, Luis A. Quinones, Hector R. Contreras
Summary: The FOLFOX scheme is commonly used for metastatic colorectal cancer patients, but chemoresistance is a major challenge. EMT and overexpression of multiple genes may contribute to drug resistance.
Article
Biochemical Research Methods
Ayalur Raghu Subbalakshmi, Sarthak Sahoo, Prakruthi Manjunatha, Shaurya Goyal, Vignesh A. Kasiviswanathan, Yeshwanth Mahesh, Soundharya Ramu, Isabelle McMullen, Jason A. A. Somarelli, Mohit Kumar Jolly
Summary: ELF3 is a factor strongly associated with an epithelial phenotype and is inhibited during EMT. It inhibits the progression of EMT and can counteract EMT induction even in the presence of EMT-inducing factors. The prognostic capacity of ELF3 is specific to cell-of-origin or lineage.
JOURNAL OF BIOLOGICAL ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Dong-Yoon Kim, Gyuryang Heo, Minyoo Kim, Hyunseo Kim, Ju Ae Jin, Hyun-Kyung Kim, Sieun Jung, Myungmo An, Benjamin H. Ahn, Jong Hwi Park, Han-Eol Park, Myungsun Lee, Jung Weon Lee, Gary J. Schwartz, Sung-Yon Kim
Article
Oncology
Jihye Ryu, Eunmi Kim, Min-Kyung Kang, Dae-Geun Song, Eun-Ae Shin, Haesong Lee, Jae Woo Jung, Seo Hee Nam, Ji Eon Kim, Hye-Jin Kim, Taekwon Son, Semi Kim, Hwi Young Kim, Jung Weon Lee
Summary: The study revealed the crucial role of TM4SF5 in the progression of nonalcoholic steatohepatitis (NASH), including inducing lipid accumulation, inflammatory responses, and fibrosis in liver tissue. TM4SF5, along with signaling pathways involving SIRT1, SREBPs, and SOCS/STAT3, promoted the development of NASH.
JOURNAL OF PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hye-Jin Kim, Eunmi Kim, Haesong Lee, Jae Woo Jung, Ji Eon Kim, Chan-Gi Pack, Jung Weon Lee
Summary: This study showed that cell adhesion to fibronectin can enhance the translocation of TM4SF5 vesicles to the leading edges, while microtubule acetylation plays a regulatory role in this process. The coordinated actions of paxillin, SLAC2B, and HDAC6 are essential for controlling the intracellular traffic of TM4SF5 vesicles towards the leading edges, leading to TM4SF5-dependent cell migration.
Article
Endocrinology & Metabolism
Cheoljun Choi, Yeonho Son, Jinyoung Kim, Yoon Keun Cho, Abhirup Saha, Minsu Kim, Hyeonyeong Im, Kyungmin Kim, Juhyeong Han, Jung Weon Lee, Je Kyung Seong, Yun-Hee Lee
Summary: TM4SF5 functions as a sensor for lysosomal arginine levels and activates mTORC1 in adipocytes. Knockout of TM4SF5 reduces mTORC1 activation, enhances autophagy and lipolysis, and promotes mitochondrial metabolism in adipose tissue, resulting in reduced adiposity and improved glucose tolerance and inflammation in response to a high-fat diet.
Article
Biochemistry & Molecular Biology
Dasomi Park, Eunmi Kim, Haesong Lee, Eun-Ae Shin, Hyejin Lee, Jung Weon Lee
Summary: TM4SF5 negatively modulates the accumulation of fatty acids in hepatocytes by associating with transporters during acute fatty acid supply, contributing to energy homeostasis.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Hyunseung Sun, Eunmi Kim, Jihye Ryu, Hyejin Lee, Eun-Ae Shin, Minhyeong Lee, Haesong Lee, Jeong-Hoon Lee, Jung-Hwan Yoon, Dae-Geun Song, Semi Kim, Jung Weon Lee
Summary: The study revealed that TM4SF5 signaling contributes to immune evasion during liver carcinogenesis by suppressing NK cell number and function. Inhibiting TM4SF5 can restore NK cell surveillance, reduce fibrotic and cancerous phenotypes, and prolong survival in liver cancer.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Sieun Jung, Myungsun Lee, Dong-Yoon Kim, Celine Son, Benjamin Hyunju Ahn, Gyuryang Heo, Junkoo Park, Minyoo Kim, Han-Eol Park, Dong-Jun Koo, Jong Hwi Park, Jung Weon Lee, Han Kyoung Choe, Sung-Yon Kim
Summary: This study demonstrates the vital role of Vgat-expressing neurons in the lateral hypothalamus (LHVgat neurons) in thermoregulatory behavior, showing that their population activity encodes thermal punishment and reward bidirectionally. The study also reveals a subpopulation of LHVgat neurons that specifically encode thermal punishment and reward, which is distinct from their encoding of caloric reward.
Article
Cell Biology
Eunmi Kim, Hyejin Um, Jinsoo Park, Jae Woo Jung, Ji Eon Kim, Haesong Lee, Eun-Ae Shin, Yangie Pinanga, Hyejin Lee, Seo Hee Nam, Jung Weon Lee
Summary: The TM4SF5 protein plays a critical role in communication between hepatocytes and macrophages, influencing the inflammatory microenvironment and potentially leading to NAFLD progression.
Article
Endocrinology & Metabolism
Hyejin Lee, Eunmi Kim, Eun-Ae Shin, Jong Cheol Shon, Hyunseung Sun, Ji Eon Kim, Jae Woo Jung, Haesong Lee, Yangie Pinanga, Dae-Geun Song, Kwang-Hyeon Liu, Jung Weon Lee
Summary: This study investigated the modulation of hepatic fructose metabolism by TM4SF5 and found that it can regulate fructose uptake and lipogenesis by interacting with GLUT8, thereby affecting liver steatosis.
MOLECULAR METABOLISM
(2022)
Article
Oncology
Dongjoon Ko, Eunmi Kim, Eun-Ae Shin, Seo Hee Nam, Junghwa Yoon, Jin-Sook Lee, Yunhee Lee, Sora Park, Kyungsoo Ha, So-Young Choi, Jung Weon Lee, Semi Kim
Summary: The study found that the antibody Ab27 can significantly inhibit the growth of tumor cells expressing TM4SF5 and reduce the levels of phosphorylated proteins associated with tumor progression. Combination therapy with other drugs can enhance the anti-tumor activity. Humanization can reduce immunogenicity while maintaining anti-tumor activity. These observations are of great significance for the further development of these antibodies as therapeutic agents against liver and colorectal cancers.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Review
Biochemistry & Molecular Biology
Ji Eon Kim, Eunmi Kim, Jung Weon Lee
Summary: Nonalcoholic fatty liver disease (NAFLD) affects up to 30% of the global population and can progress to hepatocellular carcinoma (HCC), which has a low 5-year survival rate. This review highlights the importance of specifically diagnosing and treating the co-occurrence of metabolic disorders and inflammatory environments during the development of steatohepatitis to prevent fatal HCC. The role of Transmembrane 4 L six family member 5 (TM4SF5) in regulating metabolic functions and activities in hepatocytes is discussed, as well as its potential as an NAFLD biomarker and its effects on nutrient transporters and immune cells in chronic liver diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Jae Woo Jung, Ji Eon Kim, Eunmi Kim, Hyejin Lee, Haesong Lee, Eun-Ae Shin, Jung Weon Lee
Summary: TM4SF5 is involved in chronic liver disease and its deficiency leads to age-related glucose intolerance independent of insulin sensitivity. TM4SF5 in the liver promotes glucose uptake and glycolysis, and excessive glucose causes hepatocytes to release small extracellular vesicles loaded with TM4SF5. These vesicles can target brown adipose tissues and efficiently clear high extracellular glucose levels.
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Article
Biochemistry & Molecular Biology
Joohyeong Lee, Eunmi Kim, Min-Kyung Kang, Jihye Ryu, Ji Eon Kim, Eun-Ae Shin, Yangie Pinanga, Kyung-hee Pyo, Haesong Lee, Eun Hae Lee, Heejin Cho, Jayeon Cheon, Wonsik Kim, Eek-Hoon Jho, Semi Kim, Jung Weon Lee
Summary: Overexpression of TM4SF5 exacerbates pathological abnormalities in both the colon and liver, including intestinal adenomas, carcinomas, sinusoidal dilatation, and fibrosis.
Article
Medicine, Research & Experimental
Haeng Eun Song, Yoonji Lee, Eunmi Kim, Chang Yun Cho, Oisun Jung, Doohyung Lee, Eun Goo Lee, Seo Hee Nam, Minkyung Kang, Stephani Joy Y. Macalino, Ji Eon Kim, Jae Woo Jung, Sung Won Kwon, Sun Choi, Jung Weon Lee
Summary: The study revealed that the binding of the TM4SF5 C-terminus to the kinase domain of inactive c-Src leads to its activation. Cell-penetrating peptides containing the TM4SF5 C-terminus can block the interaction of TM4SF5 with c-Src, preventing the initiation and progression of hepatocellular carcinoma.
Review
Chemistry, Medicinal
Dae-Geun Song, Eunmi Kim, Jung Weon Lee
ARCHIVES OF PHARMACAL RESEARCH
(2020)
