Review
Biochemistry & Molecular Biology
Rahul Advani, Sara Luzzi, Emma Scott, Caroline Dalgliesh, Joachim Weischenfeldt, Jennifer Munkley, David J. Elliott
Summary: This article discusses the expression of splicing regulators ESRP1 and ESRP2 in aggressively proliferating primary prostate tumors as markers of disease progression. It suggests that ESRP1 and ESRP2 act as lineage survival oncogenes in prostate cancer and highlights the need to identify the gene expression targets controlled by these regulators to develop targeted therapies.
Article
Medicine, General & Internal
Yan Zhang, Xueting Li, Yingying Gong, Danli Du, Huilei Chen, Lei Liu, Zenong Cheng
Summary: This study aimed to detect the expression of UBE2C, WNT5a, and E-cad in endometrial cancer (EC) and their clinical significance. The results showed that the positive expression of UBE2C and ZEB1 was significantly higher in EC tissues, while the positive expression of WNT5a was significantly lower. Positive expression of UBE2C and ZEB1 was associated with tumor stages, lymph node metastasis, and FIGO stages, while positive expression of E-cad was inversely related. Kaplan-Meier analyses demonstrated that positive expression of UBE2C or ZEB1 was associated with unfavorable overall survival time, while positive expression of WNT5a was associated with favorable overall survival time. Multivariate analysis identified UBE2C, WNT5a, ZEB1, and FIGO stages as independent prognostic factors for EC patients.
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)
Article
Multidisciplinary Sciences
Benjamin Nordick, Mary Chae-Yeon Park, Vito Quaranta, Tian Hong
Summary: Cooperative RNA degradation and microRNAs play an important role in generating multiple intermediate EMT states, bridging the gap between mechanistic models and single-cell experiments.
Article
Oncology
Yaoyao Xiong, Xiongbing Zu, Long Wang, Yuan Li, Minfeng Chen, Wei He, Lin Qi
Summary: The study identified lncRNA VIM-AS1 as highly expressed in bladder cancer, especially in metastatic tissues and high-metastatic cell lines. VIM-AS1 acted as a ceRNA for miR-655, competing with ZEB1 for miR-655 binding, promoting EMT in both high- and low-metastatic bladder cancer cells, and enhancing cancer cell metastasis.
CANCER CELL INTERNATIONAL
(2021)
Review
Oncology
Samantha Gogola, Michael Rejzer, Hisham F. Bahmad, Wassim Abou-Kheir, Yumna Omarzai, Robert Poppiti
Summary: Prostate cancer is the second most common cancer in men worldwide, and treatment options include radiation therapy, surgery, and active surveillance. However, in most cases, the cancer eventually becomes castration-resistant. The transition from androgen-dependent to androgen-independent state is not well understood, but epithelial-to-non-epithelial transition plays a crucial role. This review summarizes the factors and pathways involved in this transition, as well as the diagnostic and prognostic biomarkers.
Article
Biochemistry & Molecular Biology
Qing-Xiang Meng, Ke-Nie Wang, Jun-Hui Li, Hui Zhang, Zhao-Hui Chen, Xue-Jie Zhou, Xu-Chen Cao, Ping Wang, Yue Yu
Summary: The study found that ZNF384 is significantly overexpressed in breast cancer and promotes breast cancer metastasis by regulating ZEB1 expression and inducing an epithelial and mesenchymal-like phenotype. Additionally, ZNF384 may be a target of miR-485-5p, and ZEB1 can up-regulate ZNF384 expression by repressing miR-485-5p expression. These findings provide evidence for the prognostic and therapeutic potential of ZNF384 in breast cancer patients.
MOLECULAR MEDICINE
(2022)
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)
Article
Multidisciplinary Sciences
David P. Cook, Barbara C. Vanderhyden
Summary: Epithelial-mesenchymal plasticity (EMP) is closely related to tumor progression, therapy resistance and immune cell evasion. By analyzing single-cell RNA sequencing data, we found diverse EMP expression patterns within tumors, which are regulated by various mechanisms initiated from the tumor microenvironment. Inferring regulatory features can provide effective therapeutic strategies to restrict EMP.
Article
Cell Biology
Xiao Dong, Yang Han, Encheng Zhang, Yuqi Wang, Pingzhao Zhang, Chenji Wang, Lin Zhong, Qi Li
Summary: This study demonstrates that ZEB1 is a substrate of the CRL4-DCAF15 E3 ubiquitin ligase complex, with DCAF15 specifically recognizing the N-terminal zinc finger domain of ZEB1 for degradation through the ubiquitin-proteasome pathway. Knockdown of DCAF15 leads to upregulation of ZEB1 and activation of EMT in HCC, while overexpression of DCAF15 suppresses ZEB1 and inhibits EMT progression, ultimately impacting HCC cell proliferation and invasion. Low DCAF15 expression in HCC patients is associated with poor prognosis, highlighting the importance of the CUL4-DCAF15 E3 ubiquitin ligase complex in regulating ZEB1-mediated malignancy in HCC.
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
Multidisciplinary Sciences
Tianying Zheng, Wenfei Han, Aijun Wang, Yonggang Wang
Summary: This study reveals that miR-128-3p inhibits epithelial-mesenchymal transition, invasion, and migration of pancreatic cancer cells by targeting ZEB1.
Article
Cell Biology
Yan Guo, Xiaoqin Lu, Yao Chen, Geoff Clark, John Trent, Miriam Cuatrecasas, Douglas Emery, Zhao-Hui Song, Julia Chariker, Eric Rouchka, Antonio Postigo, Yongqing Liu, Douglas C. Dean
Summary: This study shows a cytoplasmic-to-nuclear transport gradient of the EMT transcription factor Zeb1 in cancer cells, which is regulated by the EMT inducer Tgfb. The transport of Zeb1 promotes the assembly of the actin cytoskeleton and cell migration. Inhibition of Zeb1 nuclear transport can suppress the malignant transition of cancer cells.
Article
Cell Biology
Dandan Wang, Liangyi Cui, Qing Yang, Jiao Wang
Summary: The up-regulated circZFPM2 in ectopic endometrial tissues can induce EMT through the miR-205-5p /ZEB1 signaling pathway, promoting cell proliferation, migration, and invasion. This may serve as a promising biomarker in the diagnosis and treatment of endometriosis.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Sergey E. Parfenyev, Sergey V. Shabelnikov, Elena N. Tolkunova, Nickolai A. Barlev, Alexey G. Mittenberg
Summary: P53 plays a critical role in protecting the genome and preventing tumor formation, including metastases. The interaction between p53 and the transcription factor Zeb1 is important in carcinogenesis, particularly in the process of epithelial to mesenchymal transition (EMT). Additionally, the composition of Zeb1 interactome is affected by the presence of cancer stem cells and the level of Oct4/Sox2 expression, indicating that stemness influences the specificity of Zeb1 interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Hector R. Contreras, Fernanda Lopez-Moncada, Enrique A. Castellon
INTERNATIONAL JOURNAL OF ONCOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Ana F. Castillo, Ulises D. Orlando, Paula M. Maloberti, Jesica G. Prada, Melina A. Dattilo, Angela R. Solano, Maria M. Bigi, Mayra A. Rios Medrano, Maria T. Torres, Sebastian Indo, Graciela Caroca, Hector R. Contreras, Belkis E. Marelli, Facundo J. Salinas, Natalia R. Salvetti, Hugo H. Ortega, Pablo Lorenzano Menna, Sergio Szajnman, Daniel E. Gomez, Juan B. Rodriguez, Ernesto J. Podesta
Summary: ACSL4 is involved in tumor aggressiveness in breast and prostate tumors, and the inhibitor PRGL493 blocks tumor growth and sensitizes cells to chemotherapy and hormonal treatment. Additionally, PRGL493 inhibits de novo steroid synthesis in cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Giacomo Canesin, Valentina Maggio, Macarena Palominos, Anna Stiehm, Hector R. Contreras, Enrique A. Castellon, Juan Morote, Rosanna Paciucci, Norman J. Maitland, Anders Bjartell, Rebecka Hellsten
SCIENTIFIC REPORTS
(2020)
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
Oncology
Gisella Perez, Fernanda Lopez-Moncada, Sebastian Indo, Maria Jose Torres, Enrique A. Castellon, Hector R. Contreras
Summary: This study demonstrated that stable silencing of ZEB1 in prostate cancer cell lines can reverse CSC properties, including decreased expression levels of CSC phenotype markers, reduced ability to form prostatospheres, and generate colonies. Targeting ZEB1 may be a key factor to eradicate CSCs and improve the prognosis of patients with advanced PCa.
Article
Biology
Catherine Sanchez, Alejandro Mercado, Hector R. Contreras, Felipe Carvajal, Apolo Salgado, Christian Huidobro, Enrique A. Castellon
Summary: The study showed that pretreatment with leuprolide and IN3 enhanced apoptosis and decreased cell survival in prostate cancer cells after radiation therapy. There was also an increased proportion of cells arrested in G2 phase.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2021)
Article
Cell Biology
Pedro Carriere, Natalia Calvo, Maria Belen Novoa Diaz, Fernanda Lopez-Moncada, Alexander Herrera, Maria Jose Torres, Exequiel Alonso, Norberto Ariel Gandini, Graciela Gigola, Hector R. Contreras, Claudia Gentili
Summary: The study shows that PTHrP modulates factors and morphological changes associated with EMT in HCT116 cells from CRC, suggesting a novel action on CRC progression involving the microenvironment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Oncology
Maria Jose Torres, Fernanda Lopez-Moncada, Daniela Herrera, Sebastian Indo, Alejandro Lefian, Paola Llanos, Julio Tapia, Enrique A. Castellon, Hector R. Contreras
Summary: The study found higher levels of ETAR expression in tissues from PCa patients with a low Gleason Score, while ETBR showed no significant changes; PC3 cells expressed higher levels of ET-1 and ETAR, while LNCaP cells exhibited higher levels of ETBR; Blocking ETAR and ETBR reduced the expression levels of steroidogenesis enzymes and AR in PC3 cells, leading to decreased T secretion.
Article
Biochemistry & Molecular Biology
Sebastian Morales-Pison, Lilian Jara, Valentina Carrasco, Cristian Gutierrez-Vera, Jose Miguel Reyes, Patricio Gonzalez-Hormazabal, Leandro J. Carreno, Julio C. Tapia, Hector R. Contreras
Summary: The rs6505162:A allele plays an important role in mammary tumorigenesis by promoting breast cancer cell proliferation, chemoresistance, migration, invasion, and inhibiting apoptosis. This finding may have implications for early diagnosis, prognosis, and treatment of breast cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Enrique A. Castellon, Sebastian Indo, Hector R. Contreras
Summary: This article explores the presence and role of cancer stem cells (CSCs) and the Epithelial-Mesenchymal transition (EMT) in prostate cancer (PCa), and finds that the stemness-mesenchymal axis is a critical process related to relapse, metastasis, and resistance. Manipulating the stemness-EMT axis genes on the androgen receptor (AR) may shed light on the effect of this axis on metastasis and castration resistance in PCa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Diego Figueroa, Javiera Rios, Oscar F. Araneda, Hector R. Contreras, Miguel L. Concha, Carlos Garcia
Summary: This study aimed to determine the acute toxicity of OA and DTX-1 on oxidative stress parameters in medaka larvae. The results showed that OA and DTX-1 significantly affected the levels of MDA and carbonyl content. DTX-1 exhibited a greater inhibition of the antioxidant system, leading to increased oxidative damage in medaka larvae.