Article
Oncology
Julie Dardare, Andrea Witz, Margaux Betz, Aurelie Francois, Morgane Meras, Laureline Lamy, Aurelien Lambert, Stephanie Grandemange, Marie Husson, Marie Rouyer, Jessica Demange, Jean-Louis Merlin, Alexandre Harle, Pauline Gilson
Summary: This study investigates the role of DDB2 in pancreatic ductal adenocarcinoma (PDAC). The results show that lower expression of DDB2 is associated with shorter disease-free survival in PDAC patients. Overexpression of DDB2 can decrease cell migration and invasion, and increase sensitivity to certain chemotherapy drugs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Agnes Czikora, Katalin Erdelyi, Tamas Ditroi, Noemi Szanto, Eszter Petra Juranyi, Szilard Szanyi, Jozsef Tovari, Tamas Strausz, Peter Nagy
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with increasing incidence globally. This study found that the expression levels of cystathionine beta-synthase (CBS) are elevated in metastatic PDAC cells compared to non-metastatic primary tumors. Further investigations revealed that CBS plays a significant role in cancer cell invasion and metastasis, potentially through its involvement in epithelial to mesenchymal transition (EMT) of the cells.
Review
Biochemistry & Molecular Biology
Roman Bubin, Romans Uljanovs, Ilze Strumfa
Summary: The discovery of cancer stem cells (CSCs) in leukemia has led to active research on stemness in neoplastic tissues. CSCs are a subpopulation of malignant cells with unique properties, including a dedifferentiated state, self-renewal, pluripotency, resistance to therapy, epigenetic alterations, and higher tumorigenicity. CSCs have been confirmed in various malignancies, including pancreatic ductal adenocarcinoma, which has a poor prognosis. This review aims to summarize the current knowledge on the markers and molecular features of CSCs in pancreatic ductal adenocarcinoma and the therapeutic options for their elimination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tugba Mehmetoglu-Gurbuz, Rajkumar Lakshmanaswamy, Karla Perez, Mayra Sandoval, Casandra A. Jimenez, Jackelyn Rocha, Rachel Madeline Goldfarb, Courtney Perry, Alejandra Bencomo, Nishkala Neela, Jose A. Barragan, Raquel Sanchez, Risa Mia Swain, Ramadevi Subramani
Summary: This study found that nimbolide (NB) effectively blocks the growth and metastasis of pancreatic ductal adenocarcinomas (PDACs) by suppressing the expression and activity of superoxide dismutase 2 (SOD2). NB induces high levels of reactive oxygen species (ROS) generation, leading to increased apoptosis and reduced progression of PDACs. SOD2 plays an important role in regulating NB-induced ROS generation, presenting itself as a therapeutic option for PDACs.
Article
Oncology
Yujin Pan, Deyu Li, Jiuhui Yang, Ning Wang, Erwei Xiao, Lianyuan Tao, Xiangming Ding, Peichun Sun, Dongxiao Li
Summary: This study demonstrates the preferability of portal venous for CTC testing and the association of high PoV M-CTC count with increased risk of metastasis and shorter survival time in resectable PDAC patients. PoV CTC phenotype detection shows potential as a reliable and accurate tool for identifying high-risk PDAC patients for better management strategies.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Kostas Palamaris, Evangelos Felekouras, Stratigoula Sakellariou
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy characterized by aggressive behavior and resistance to chemotherapy, with emerging evidence pointing to epithelial to mesenchymal transition (EMT) as a key driver of disease progression and drug resistance. EMT allows cancer cells to transition to a more mesenchymal state, contributing to tumor dissemination and chemoresistance in PDAC.
Article
Oncology
Xin Zhao, Xiaoshi Zhang, Xinxue Zhang, Tao Jiang, Jialei Zhai, Huaguang Wang, Mengxiu Huang, Ren Lang, Qiang He
Summary: This study revealed that miR-374b-5p is downregulated in pancreatic cancer (PC) and its overexpression can inhibit the proliferation, migration, and invasion of PC cells by suppressing the expression of KDM5B, thereby reducing epithelial-mesenchymal transition (EMT) in PC. The findings suggest that miR-374b-5p could potentially serve as a prognostic biomarker and therapeutic target for EMT induced by KDM5B in PC.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Cell Biology
Yuzheng Xue, Tielong Wu, Yingyue Sheng, Yao Zhong, Benshun Hu, Chuanqing Bao
Summary: MiR-1252-5p is downregulated in PAC and may act as a tumor-suppressing miRNA, affecting the biological behaviors of PAC through regulating the SRC/STAT3 pathway and NEDD9.
Article
Cell Biology
Cheng Xiong, Youwei Zhu, Meilin Xue, Yongsheng Jiang, Yiming Zhong, Lingxi Jiang, Minmin Shi, Hao Chen
Summary: This study revealed that TAMs promote PDAC progression through the TGF-beta signaling pathway, and the pro-tumorigenic effects of TAMs or TAM-CM can be abolished by inhibiting the TGF-beta signaling pathway or neutralizing TGF-beta antibody.
Review
Biochemistry & Molecular Biology
Hitomi Fujisaki, Sugiko Futaki
Summary: The epithelial-mesenchymal transition (EMT) is a biological process observed during development, wound healing, and cancer invasion. Factors such as growth factor stimulation and adhesion to collagen induce EMT in cancer cells. Collagen I (Col-I) can form gel structures, and its gel formation state affects EMT induction. This study reviews the relationship between Col-I gel-forming states and EMT induction in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Mortoglou, Francesc Miralles, Elif Damla Arisan, Alwyn Dart, Stipo Jurcevic, Sigrun Lange, Pinar Uysal-Onganer
Summary: This study investigated the role of miR-21 in cancer stem cells (CSCs) and its association with the aggressiveness of PDAC. Knockout of miR-21 resulted in reversed expressions of CSC markers and suppressed cellular invasion and proliferation. These findings suggest that miR-21 is involved in the stemness of PDAC cells, may play roles in mesenchymal transition, and serves as a novel functional biomarker for PDAC aggressiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Marie-Lucie Racu, Laetitia Lebrun, Andrea Alex Schiavo, Claude Van Campenhout, Sarah De Clercq, Lara Absil, Esmeralda Minguijon Perez, Calliope Maris, Christine Decaestecker, Isabelle Salmon, Nicky D'Haene
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and its incidence is increasing over time. Understanding the molecular mechanisms behind metastasis and chemoresistance in PDAC is crucial, as these are the main causes of death in patients. SMAD4 is deactivated in half of PDAC cases and its loss is associated with worse overall survival and metastasis. SMAD4 is a key transducer in the TGF-beta pathway, which plays a role in epithelial-mesenchymal transition (EMT). EMT is a biological process where epithelial cells lose their characteristics and acquire a more mesenchymal phenotype, leading to increased motility. Recent studies suggest that cells may undergo intermediate states during EMT, known as epithelial-mesenchymal plasticity (EMP), which exhibit enhanced aggressiveness and more efficient metastasis. This review aims to summarize and analyze current knowledge on SMAD4 loss in PDAC patients and investigate its potential role in EMP, in order to better understand its function in PDAC carcinogenesis.
Article
Biochemistry & Molecular Biology
Kai-Zhou Jin, Ying Wu, Xiao-Xiao Zheng, Tian-Jiao Li, Zhen-Yu Liao, Qing-Lin Fei, Hui-Ru Zhang, Sai-Meng Shi, Xin Sha, Xian-Jun Yu, Wei Chen, Long-Yun Ye, Wei-Ding Wu
Summary: Intrinsic drug resistance mechanisms in tumor cells and epithelial-to-mesenchymal transition (EMT) significantly reduce the effectiveness of cancer treatment. This study developed cSN38 nanoparticles and a TGF-beta 1 inhibitor, LY364947, as a strategy to overcome drug resistance in pancreatic ductal adenocarcinoma (PDAC). The combination of cSN38 and LY364947 nanoparticles improved drug sensitivity, reduced EMT, and inhibited PDAC tumor growth both in vitro and in vivo. These findings highlight the potential of nanoscale therapeutics in combating PDAC.
Article
Health Care Sciences & Services
Constantin Busuioc, Cristina Alexandra Ciocan-Cartita, Cornelia Braicu, Oana Zanoaga, Lajos Raduly, Monica Trif, Mihai-Stefan Muresan, Calin Ionescu, Cristina Stefan, Carmen Crivii, Nadim Al Hajjar, Simona Margarit, Ioana Berindan-Neagoe
Summary: The study utilized bioinformatics approaches to investigate alterations in EMT-related genes in colon adenocarcinoma patients, identifying key gene changes related to prognosis in COAD. These findings may help develop biomarkers for recurrence prediction in COAD patients and improve risk stratification for patients.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ching-Chung Ko, Yao-Yu Hsieh, Pei-Ming Yang
Summary: Epithelial-to-mesenchymal transition (EMT) is a biological process that promotes cancer cell dissemination and drug resistance. This study revealed that overexpression of MIR31HG in pancreatic ductal adenocarcinoma (PDAC) patients is associated with poorer disease-free survival, as well as upregulation of genes related to TGF beta signaling and EMT. In vitro experiments further demonstrated that TGF beta induces MIR31HG expression and knockdown of MIR31HG reverses TGF beta-induced EMT phenotypes and cancer cell migration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hannah Swahn, Jey Sabith Ebron, Kay-Marie Lamar, Shiyi Yin, Jenny L. Kerschner, Monali NandyMazumdar, Candice Coppola, Eric M. Mendenhall, Shih-Hsing Leir, Ann Harris
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2019)
Article
Biochemistry & Molecular Biology
Monali NandyMazumdar, Shiyi Yin, Alekh Paranjapye, Jenny L. Kerschner, Hannah Swahn, Alex Ge, Shih-Hsing Leir, Ann Harris
NUCLEIC ACIDS RESEARCH
(2020)
Article
Physiology
Alekh Paranjapye, Michael J. Mutolo, Jey Sabith Ebron, Shih-Hsing Leir, Ann Harris
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2020)
Article
Cell Biology
Shih-Hsing Lei, Shiyi Yin, Enny L. Kerschne, Sunny Xia, Saumel Ahmadi, Christine Bear, Ann Harris
CELL AND TISSUE RESEARCH
(2020)
Article
Cell Biology
Shiyi Yin, Greeshma Ray, Jenny L. Kerschner, Shuyu Hao, Aura Perez, Mitchell L. Drumm, James A. Browne, Shih-Hsing Leir, Michelle Longworth, Ann Harris
PHYSIOLOGICAL GENOMICS
(2020)
Article
Cell Biology
Jenny L. Kerschner, Alekh Paranjapye, Shiyi Yin, Dannielle L. Skander, Gurkan Bebek, Shih-Hsing Leir, Ann Harris
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2020)
Article
Biology
Shih-Hsing Leir, Shiyi Yin, Jenny L. Kerschner, Wilmel Cosme, Ann Harris
LIFE SCIENCE ALLIANCE
(2020)
Article
Anatomy & Morphology
Jenny L. Kerschner, Alekh Paranjapye, Monali NandyMazumdar, Shiyi Yin, Shih-Hsing Leir, Ann Harris
Summary: This study using human induced pluripotent stem cells differentiated into airway epithelial cells identified novel open chromatin regions that impact CFTR expression during early endoderm differentiation. OTX2 plays a key role in regulating CFTR expression by recruiting cis-regulatory elements to the locus.
DEVELOPMENTAL DYNAMICS
(2021)
Article
Cell Biology
James A. Browne, Monali NandyMazumdar, Alekh Paranjapye, Shih-Hsing Leir, Ann Harris
Summary: The study investigated the role of Bromodomain Containing 8 (BRD8) in coordinating lung epithelial function, revealing its involvement in innate immune response and cell cycle regulation. Depletion of BRD8 increased secretion of antimicrobial peptide beta-defensin 1 and chemokines, while reducing cell proliferation.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alekh Paranjapye, Monali NandyMazumdar, James A. Browne, Shih-Hsing Leir, Ann Harris
Summary: This study characterizes the role of KLF5 in controlling essential pathways of epithelial cell identity and function in the human lung. Results show that KLF5 plays a key role in regulating genes involved in cell adhesion and proinflammatory response, highlighting its pivotal role in coordinating epithelial functions relevant to human lung disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Monali NandyMazumdar, Alekh Paranjapye, James Browne, Shiyi Yin, Shih-Hsing Leir, Ann Harris
Summary: The CFTR gene is regulated by multiple CREs and TFs within a TAD, with BACH1 playing a significant role in fine-tuning expression through direct activation under normal conditions and indirect modulation under oxidative stress. BACH1 also directly regulates CFTR gene expression by modulating the higher order chromatin structure of the gene.
BIOCHEMICAL JOURNAL
(2021)
Article
Cell Biology
Alekh Paranjapye, Shih-Hsing Leir, Felix Huang, Jenny L. Kerschner, Ann Harris
Summary: By using single-cell RNA sequencing, we studied different cell populations in the human respiratory tract and male genital ducts, and identified shared differentiated functions among them. Furthermore, we found differences in cell type distribution between cystic fibrosis patients and healthy donors. We also observed overlapping gene expression patterns of basal and secretory cell populations in different anatomical sites.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Umida Burkhanova, Ann Harris, Shih-Hsing Leir
Summary: The cross-talk between lung epithelial cells and their microenvironment is crucial for maintaining the state of lung progenitor cells. In this study, an in vitro model was used to investigate the contribution of the microenvironment to the differentiation of induced pluripotent stem cells (iPSCs) to lung epithelial cells. The results showed that the type of basement membrane protein coating and co-culture with pulmonary microvascular endothelial cells (HPMECs) had significant effects on the differentiation of iPSCs to lung epithelial cells.
STEM CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Arnaud J. Van Wettere, Shih-Hsing Leir, Calvin U. Cotton, Misha Regouski, Iuri Viotti Perisse, Jenny L. Kerschner, Alekh Paranjapye, Zhiqiang Fan, Ying Liu, Makayla Schacht, Kenneth L. White, Irina A. Polejaeva, Ann Harris
Summary: Highly effective modulator therapies make CF a treatable condition. Using an ovine model, the study investigates the in utero origins of CF disease and finds that CF already causes damage in the digestive tract and respiratory system before birth. The study also shows that CFTR (-/-) tissues exhibit histological abnormalities by 80 days of gestation, equivalent to 21 weeks in humans.
Article
Biochemistry & Molecular Biology
Iuri Viotti Perisse, Zhiqiang Fan, Arnaud Van Wettere, Ying Liu, Shih-Hsing Leir, Jacob Keim, Misha Regouski, Michael D. Wilson, Kelly M. Cholewa, Sara N. Mansbach, Thomas J. Kelley, Zhongde Wang, Ann Harris, Kenneth L. White, Irina A. Polejaeva
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene. Researchers have successfully generated CF lamb models using CRISPR/Cas9 and SCNT. These models can be used to test new CF treatments and gene therapies to improve the health of patients.