Article
Oncology
Andreia S. Margarido, Rebeca Uceda-Castro, Kerstin Hahn, Roebi de Bruijn, Lennart Kester, Ingrid Hofland, Jeroen Lohuis, Danielle Seinstra, Annegien Broeks, Jos Jonkers, Marike L. D. Broekman, Pieter Wesseling, Claire Vennin, Miguel Vizoso, Jacco van Rheenen
Summary: The study demonstrates that breast cancer brain metastasis cells undergo epithelial-to-mesenchymal transition (EMT) when infiltrating the brain parenchyma, and removing these infiltrated tumor cells can improve surgical efficacy, providing new avenues for patient treatment.
Article
Oncology
Rosemary J. Akhurst
Summary: Epithelial-to-mesenchymal transition (EMT) is a cell shape-changing process that plays a critical role in embryogenesis and disease progression. It is influenced by extracellular factors and intracellular signaling pathways. EMT is associated with tumor progression, development of a stem-like cell state, and drug resistance.
SEMINARS IN CANCER BIOLOGY
(2023)
Article
Cell Biology
Buse Cevatemre, Engin Ulukaya, Egemen Dere, Sukru Dilege, Ceyda Acilan
Summary: There has been growing interest in the role of mitochondria in metastatic cascade. This study demonstrates that inhibiting PDH can induce EMT and result in chemoresistance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Annie Cristhine Moraes Sousa-Squiavinato, Diego Alfonso Arregui Ramos, Monica Silveira Wagner, Josiane Weber Tessmann, Julio Cesar Madureira de-Freitas-Junior, Jose Andres Morgado-Diaz
Summary: A long-term drug-resistant colorectal cancer model was established to explore the cellular events underlying 5-fluorouracil (5FU) resistance. The study identified various cellular events and molecular changes associated with 5FU resistance, as well as specific genes that could predict poor outcomes in colorectal cancer patients. The findings highlight the importance of identifying promising targets involved in multiple cellular events to overcome drug resistance.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Oncology
Xirui Duan, Maochao Luo, Jian Li, Zhisen Shen, Ke Xie
Summary: This review discusses the role of platinum-based drugs (PBDs)-induced epithelial-mesenchymal transition (EMT) in cancer drug resistance and emphasizes how this novel knowledge can be exploited to overcome PBD resistance, particularly through EMT-targeted compounds.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jingyu Kuang, Ting Duan, Changsong Gao, Chuanyang Liu, Si Chen, Lv-yun Zhu, Lu Min, Chenyu Lu, Wenlun Wang, Lingyun Zhu
Summary: In this study, the expression of RNF8 was found to be up-regulated in HCC tissues and positively correlated with poor prognosis of HCC. Silencing RNF8 attenuated the migration of HCC cells and inhibited EMT by regulating the expressions of specific proteins. High RNF8 expression predicted poor survival benefits from sorafenib, and RNF8 depletion enhanced the sensitivity of HCC cells to sorafenib and lenvatinib treatment.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
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
Biochemistry & Molecular Biology
Fu Peng, Huali Fan, Sui Li, Cheng Peng, Xiaoqi Pan
Summary: MicroRNAs have been utilized as negative regulators in cancer treatment by down-regulating their targets, especially in the EMT process. Natural plant compounds can modulate deregulated microRNAs to inhibit EMT, which could potentially lead to the inhibition of cancer development. This review article highlights the significance of microRNAs in EMT as oncogenes and tumor suppressor genes, providing evidence for target therapy in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Stefano Zapperi, Caterina A. M. La Porta
Summary: Finding prognostic and predictive markers for TNBC is highly desirable, and the recently developed transcriptomic test ARIADNE shows promising capabilities in this regard.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Diana Duarte, Alexandra Rema, Irina Amorim, Nuno Vale
Summary: Despite research advancement in drug therapy for solid tumors, cancer remains a major health problem. Drug repurposing and combination strategies have gained interest. A novel drug combination using different CNS drugs and DOX was proposed and studied in MCF-7 breast cancer cells. Immunohistochemistry results suggest that these treatments could induce EMT reversal.
Article
Biochemistry & Molecular Biology
Baris Kucukkaraduman, Ekin Gokce Cicek, Muhammad Waqas Akbar, Secil Demirkol Canli, Burcak Vural, Ali Osmay Gure
Summary: This study investigated the use of eight natural compounds and two repurposed agents on cancer cells, with curcumin showing the most significant anti-cancer activity across different cell lines. While some natural products induced MET in cancer cells, the MET induction did not necessarily enhance chemosensitivity.
Article
Oncology
Kakeru Hisakane, Masahiro Seike, Teppei Sugano, Akiko Yoshikawa, Kuniko Matsuda, Natsuki Takano, Satoshi Takahashi, Rintaro Noro, Akihiko Gemma
Summary: Exosomal miR-210-3p plays a crucial role in resistance to osimertinib in EGFR-mutant NSCLC, by promoting epithelial-mesenchymal transition (EMT) and inducing drug resistance. Further studies are needed to explore the potential of targeting miR-210-3p as a therapeutic strategy for overcoming osimertinib resistance in NSCLC.
Review
Oncology
Nicholas S. Mastronikolis, Efthymios Kyrodimos, Despoina Spyropoulou, Alexander Delides, Evangelos Giotakis, Zoi Piperigkou, Nikos K. Karamanos
Summary: Exosomes are nanosized vesicles produced by cells that play important roles in head and neck cancer development and metastasis by altering signaling pathways in recipient cells through the cargoes they carry. This article focuses on exosome biogenesis, their cargoes, and their involvement in epithelial-to-mesenchymal transition (EMT) induction and metastasis in head and neck cancer. It also discusses the key role of exosomes in extracellular matrix remodeling and degradation, and their potential as diagnostic and therapeutic tools.
Article
Medicine, Research & Experimental
Dilys Leung, Zoe K. Price, Noor A. Lokman, Wanqi Wang, Lizamarie Goonetilleke, Elif Kadife, Martin K. Oehler, Carmela Ricciardelli, George Kannourakis, Nuzhat Ahmed
Summary: The study identified novel EMT-related markers in platinum-resistant ovarian cancer cells, indicating a potential link between EMT and chemotherapy resistance. Proteomic analysis revealed enhanced cell migration and reduced proliferation, glycolysis, and oxidative phosphorylation in resistant cell lines.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Qizhi Wang, Ming Wu, Haobin Li, Xin Rao, Luyao Ao, Huan Wang, Lan Yao, Xinyu Wang, Xiaodan Hong, Jun Wang, Jiye Aa, Minjie Sun, Guangji Wang, Jiali Liu, Fang Zhou
Summary: This study investigates the common mechanisms of drug resistance and epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) from the perspective of metabolic reprogramming. It identifies GLUD1 as a key determinant of glutamine addiction in acquired resistant NSCLC cells, and shows that GLUD1-mediated alpha-KG production and ROS accumulation primarily trigger migration and invasion. Pharmacological and genetic interference with GLUD1 reverses drug resistance and decreases cell migration and invasion capability. The successful application of a GLUD1 inhibitor overcomes both acquired resistance and EMT-induced metastasis in vivo, demonstrating GLUD1 as a promising therapeutic target for NSCLC progression.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Immunology
Xuezhen Zeng, Jingying Zhou, Zhewen Xiong, Hanyong Sun, Weiqin Yang, Myth T. S. Mok, Jing Wang, Jingqing Li, Man Liu, Wenshu Tang, Yu Feng, Hector Kwong-Sang Wang, Shun-Wa Tsang, King-Lau Chow, Philip Chun Yeung, John Wong, Paul Bo-San Lai, Anthony Wing-Hung Chan, Ka Fai To, Stephen Lam Chan, Qiang Xia, Jing Xue, Xiao Chen, Jun Yu, Sui Peng, Joseph Jao-Yiu Sung, Ming Kuang, Alfred Sze-Lok Cheng
Summary: This study demonstrates that aberrantly activated CCRK signaling in chronic liver diseases can reprogram the immunosuppressive microenvironment to promote cancer metastasis to the liver. Overexpression of CCRK increases the metastasis of melanoma and colorectal cancer to the liver, while depletion of these signals reduces the risk of metastasis.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Cell Biology
Hung Chan, Qing Li, Xiansong Wang, Wing Yingzhi Liu, Wei Hu, Judeng Zeng, Chuan Xie, Thomas Ngai Yeung Kwong, Idy Hiu Ting Ho, Xiaodong Liu, Huarong Chen, Jun Yu, Ho Ko, Raphael Chiu Yeung Chan, Margaret Ip, Tony Gin, Alfred Sze Lok Cheng, Lin Zhang, Matthew Tak Vai Chan, Sunny Hei Wong, William Ka Kei Wu
Summary: Clostridioides difficile infection (CDI) is a common cause of nosocomial diarrhea. TcdB impairs lysosomal function in macrophages, leading to inflammation. Vitamin D-3 and carbamazepine protect against CDI by restoring lysosomal function and the expression of the transcription factor MITF in macrophages.
Article
Oncology
Feng Wu, Liangliang Xu, Yalin Tu, Otto K. W. Cheung, Lemuel L. M. Szeto, Myth T. S. Mok, Weiqin Yang, Wei Kang, Qin Cao, Paul B. S. Lai, Stephen L. Chan, Patrick Tan, Joseph J. Y. Sung, Kevin Y. Yip, Alfred S. L. Cheng, Ka F. To
Summary: This study identified an average of about 500 somatically-acquired super-enhancers per patient in non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinomas (HCCs), which were functionally enriched for aberrant metabolism and cancer phenotypes. Particularly, SIRT7 played a crucial role in HCC, affecting chromatin regulatory network and potentially serving as a druggable vulnerability.
Article
Chemistry, Multidisciplinary
Philip Chiu-Tsun Tang, Jeff Yat-Fai Chung, Vivian Wei-wen Xue, Jun Xiao, Xiao-Ming Meng, Xiao-Ru Huang, Shuang Zhou, Alex Siu-Wing Chan, Anna Chi-Man Tsang, Alfred Sze-Lok Cheng, Tin-Lap Lee, Kam-Tong Leung, Eric W-F Lam, Ka-Fai To, Patrick Ming-Kuen Tang, Hui-Yao Lan
Summary: This study identified a novel role of macrophage-myofibroblast transition (MMT) in cancer, showing that MMT cells can de novo generate cancer-promoting cancer-associated fibroblasts (CAFs). Through fate-mapping, RNA velocity, and pseudotime analysis, a subset of CAFs derived from macrophages was confirmed in the tumor microenvironment. Targeting Smad3, a key regulator in the MMT process, effectively blocked CAF formation and cancer progression in vivo, suggesting MMT as a potential therapeutic target for cancer immunotherapy.
Article
Oncology
Xiansong Wang, Wei Hu, Xiangchun Li, Dan Huang, Qing Li, Hung Chan, Judeng Zeng, Chuan Xie, Huarong Chen, Xiaodong Liu, Tony Gin, Maggie Haitian Wang, Alfred Sze Lok Cheng, Wei Kang, Ka-Fai To, Dariusz Plewczynski, Qingpeng Zhang, Xiaoting Chen, Danny Cheuk Wing Chan, Ho Ko, Sunny Hei Wong, Jun Yu, Matthew Tak Vai Chan, Lin Zhang, William Ka Kei Wu
Summary: This study reveals that X-linked tumor suppressor genes (TSGs) are under negative selection and have experienced extensive relocation from the X chromosome to autosomes during evolution. X-linked TSGs in mammals are younger or larger in size, and exhibit more frequent nonsynonymous somatic mutations, potentially conferring a survival advantage by evading single-hit inactivation.
Article
Gastroenterology & Hepatology
Xuezhen Zeng, Guanrui Liao, Shumin Li, Haining Liu, Xiao Zhao, Shuang Li, Kai Lei, Shenghua Zhu, Zhihang Chen, Yi Zhao, Xuxin Ren, Tianhong Su, Alfred Sze-Lok Cheng, Sui Peng, Shuibin Lin, Ji Wang, Shuling Chen, Ming Kuang
Summary: METTL1 plays a role in shaping the immunosuppressive tumor microenvironment after insufficient RFA, influencing tumor recurrence and treatment efficacy.
Article
Oncology
Tian Liu, Yubing Wang, Yiwei Wang, Stanley Kwok-Kuen Cheung, Penelope Mei-Yu Or, Chi-Wai Wong, Jingyu Guan, Zhining Li, Weiqin Yang, Yalin Tu, Jing Wang, Wayne Lut-Heng Ho, Haiwei Gu, Alfred Sze-Lok Cheng, Stephen Kwok-Wing Tsui, Andrew M. Chan
Summary: Weighted gene co-expression network analysis (WGCNA) identified a cell-cycle module associated with poor prognosis and aggressiveness of glioma. Within this module, Regulator of chromatin condensation 2 (RCC2) serves as a core member and plays a vital role in the mitotic process. Abnormal RCC2 expression is involved in cancer development. Gene silencing experiments confirm the importance of RCC2 in glioma cell proliferation and migration. RNA-Sequencing analysis reveals that RCC2 has a dual role in the cell cycle and metabolism.
Article
Biotechnology & Applied Microbiology
Xiaoyu Liu, Jingying Zhou, Haoran Wu, Shufen Chen, Lingyun Zhang, Wenshu Tang, Liang Duan, Ying Wang, Eleanor McCabe, Mengying Hu, Zhuo Yu, Hanzhuang Liu, Chung Hang Jonathan Choi, Joseph Jao-yiu Sung, Leaf Huang, Rihe Liu, Alfred Sze-lok Cheng
Summary: The local microenvironment where tumors develop can affect cancer progression and treatment outcomes. In hepatocellular carcinoma (HCC), which often develops in a liver fibrotic environment, nanodelivery of a PD-L1 trap gene shows superior efficacy compared to conventional monoclonal antibodies in treating fibrosis-associated HCC.
Editorial Material
Gastroenterology & Hepatology
Alfred Sze-Lok Cheng
Article
Gastroenterology & Hepatology
Zhiwu Tan, Mei Sum Chiu, Xinxiang Yang, Ming Yue, Tan To Cheung, Dongyan Zhou, Yuewen Wang, Anthony Wing-Hung Chan, Chi Wing Yan, Ka Yi Kwan, Yik Chun Wong, Xin Li, Jingying Zhou, Ka Fai To, Jiye Zhu, Chung Mau Lo, Alfred Sze-Lok Cheng, Stephen Lam Chan, Li Liu, You-Qiang Song, Kwan Man, Zhiwei Chen
Summary: A PD-1 isoform called Delta 42PD-1 plays an important role in the development and resistance to nivolumab immune checkpoint blockade (ICB) in hepatocellular carcinoma (HCC). We investigated the role of Delta 42PD-1 in HCC patients and found that Delta 42PD-1(+) T cells accounted for up to 71% of cytotoxic T lymphocytes in untreated HCC patients and were associated with HCC severity. These Delta 42PD-1(+) T cells were more exhausted than PD-1(+) T cells. HCC patients treated with anti-PD-1 ICB showed increased frequencies of Delta 42PD-1(+) T cells over time, especially in patients with progressive disease. Delta 42PD-1(+) T cells sustained HCC through toll-like receptor 4 signaling. An anti-Delta 42PD-1 antibody inhibited tumor growth in murine HCC models.
Article
Chemistry, Medicinal
Ping Sun, Jing Wang, Khadija S. Khan, Weiqin Yang, Billy Wai-Lung Ng, Nikita Ilment, Matthes Zessin, Emre F. Buelbuel, Dina Robaa, Frank Erdmann, Matthias Schmidt, Christophe Romier, Mike Schutkowski, Alfred Sze-Lok Cheng, Wolfgang Sippl
Summary: This study identifies a HDAC8 inhibitor with T cell modulatory properties and demonstrates its potential in reducing hepatocellular carcinoma tumorigenicity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Ping Gu, Kai Ding, Lei Lu, Yu Zhang, Wei Wang, Qingyu Guo, Yannian Liao, Bingjie Yang, Tiantian Wang, Changsheng Zhou, Bin Lu, Alice P. S. Kong, Alfred S. Cheng, Hannah Xiaoyan Hui, Jiaqing Shao
Summary: This study investigated the expressions of major brown adipose markers in white adipose tissue (WAT) of different ages and their associations with metabolic parameters and key adipokines. The findings suggest that UCP1 and PRDM16 have differential clinical correlations with metabolic features in human WAT in an age-dependent manner. UCP1 and PRDM16 may participate in the pathogenesis of ageing-related metabolic diseases with distinct mechanisms.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Yalin Tu, Zhewen Xiong, Chengpeng Zhong, Haoran Wu, Jing Wang, Patrick Pak-Chun Wong, Weiqin Yang, Jingying Zhou, Ka-Fai To, Joseph Sung, Stephen Lam Chan, David Kerr, Nick La Thangue, Alfred Sze-Lok Cheng
Article
Medicine, Research & Experimental
Yifei Wang, Huarong Chen, Weixin Liu, Huan Yan, Yihan Zhang, Alvin H. K. Cheung, Jinglin Zhang, Bonan Chen, Li Liang, Zhaocai Zhou, Chi Chun Wong, William K. K. Wu, Michael W. Y. Chan, Alfred S. L. Cheng, Brigette B. Y. Ma, Jun Yu, Kwok Wai Lo, Ka Fai To, Wei Kang
Summary: This study reveals the importance of the YAP-MCM6 axis in gastric cancer, where YAP hyperactivation induces MCM6 transcription. Increased expression of MCM6 is associated with poor prognosis in gastric cancer patients and promotes the proliferation and metastasis of gastric cancer cells through the PI3K/Akt signaling pathway. Inhibition of MCM6 suppresses gastric cancer growth and enhances sensitivity to genotoxic agents by modulating the ATR/Chk1-dependent DNA damage response.
Article
Immunology
Wenshu Tang, Jingying Zhou, Weiqin Yang, Yu Feng, Haoran Wu, Myth T. S. Mok, Lingyun Zhang, Zhixian Liang, Xiaoyu Liu, Zhewen Xiong, Xuezhen Zeng, Jing Wang, Jiahuan Lu, Jingqing Li, Hanyong Sun, Xiaoyu Tian, Philip Chun Yeung, Yong Hou, Heung Man Lee, Candice C. H. Lam, Howard H. W. Leung, Anthony W. H. Chan, Ka Fai To, John Wong, Paul B. S. Lai, Kelvin K. C. Ng, Simon K. H. Wong, Vincent W. S. Wong, Alice P. S. Kong, Joseph J. Y. Sung, Alfred S. L. Cheng
Summary: Obesity and hypercholesterolemia are major risk factors for hepatocellular carcinoma. This study found that obesity leads to hepatic cholesterol accumulation, which suppresses natural killer T (NKT) cell-mediated antitumor immunosurveillance. By lowering cholesterol and inhibiting cholesterol biosynthesis, the function of NKT cells can be restored to prevent HCC development promoted by obesity.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
