Article
Oncology
Meng Luo, Jinfan Li, Qi Yang, Song Xu, Kun Zhang, Jing Chen, Suzhan Zhang, Shu Zheng, Jiaojiao Zhou
Summary: This study identifies N4BP3 as a new regulator that promotes breast cancer metastasis by regulating the ubiquitination and degradation of E-cadherin. It uncovers an unprecedented role for N4BP3 in breast cancer metastasis and elucidates the underlying molecular mechanisms.
Article
Cell Biology
Xiaoqing Wan, Jiaxin Hou, Shurong Liu, Yanli Zhang, Wenqing Li, Yanru Zhang, Yi Ding
Summary: Resistance to anthracyclines, such as doxorubicin, is commonly observed in ER alpha-positive breast cancer patients. EMT plays a role in chemotherapy-induced drug resistance, with ER alpha-positive cells showing lower sensitivity to doxorubicin compared to ER alpha-negative cells. The regulation of E-cadherin expression in response to doxorubicin treatment varies depending on ER alpha status, with potential implications for treatment strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
John Alexander, Odette Mariani, Celine Meaudre, Laetitia Fuhrmann, Hui Xiao, Kalnisha Naidoo, Andrea Gillespie, Ioannis Roxanis, Anne Vincent-Salomon, Syed Haider, Rachael Natrajan
Summary: This study found that invasive lobular breast cancers with heterogeneous E-cadherin expression are composed of different components with a common ancestor. CDH1 gene mutations and loss of E-cadherin protein expression are characteristic of these tumors. Regardless of E-cadherin protein expression, these tumors should be considered part of the spectrum of invasive lobular breast cancers.
Article
Oncology
Serena Bertozzi, Ambrogio P. Londero, Luigi Viola, Maria Orsaria, Michela Bulfoni, Stefania Marzinotto, Bruna Corradetti, Umberto Baccarani, Daniela Cesselli, Carla Cedolini, Laura Mariuzzi
Summary: TFEB, SIRT1, and Beclin-1 may have potential prognostic significance in patients with chemo-treated breast cancer, likely due to their role in regulating autophagy. Additionally, no correlation was found between TFEB and PITX2 methylation, likely because they each have distinct roles in the autophagy process.
Article
Oncology
Xiaoyan Bai, Xiao Jiang, Yuting Liu, Yiting Wang, Xuewei Jiang, Guang Song, Hongmei Qiu, Qinggao Zhang
Summary: The aberrant expression of KLF9 is frequently found in certain types of cancer and is implicated in cancer initiation and progression. This study demonstrated that KLF9 inhibits breast cancer cell migration and invasion by activating the E-cadherin promoter. KLF9 also suppresses lung metastasis of breast cancer and upregulates E-cadherin expression in breast cancer cells, providing new insights into potential aggressive treatment strategies for breast cancer targeting the KLF9/E-cadherin axis.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Oncology
Giuseppina Daniela Naimo, Martina Forestiero, Alessandro Paoli, Rocco Malivindi, Luca Gelsomino, Balazs Gyorffy, Adele Elisabetta Leonetti, Francesca Giordano, Salvatore Panza, Francesca Luisa Conforti, Paola Ruffo, Maria Luisa Panno, Loredana Mauro, Sebastiano Ando
Summary: Adiponectin enhances ERa-positive breast cancer cell growth and distant metastasis by promoting E-cadherin expression and altering cell polarity through the ERa/LKB1 complex. The presence of E-cadherin is crucial for the proliferative effects of adiponectin on breast cancer cells. Furthermore, adiponectin treatment leads to the colocalization of LKB1 and Cdc42 in the nucleus, impairing their cytosolic cooperation in maintaining cell polarity. These findings highlight the importance of adiponectin in breast cancer progression and metastasis.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Ahlam M. M. Alhusaini, Sara A. A. Alhumaidan, Ghaida M. M. Alharbi, Eman A. A. Alzahrani, WedadS S. Sarawi, Hatun A. A. Alomar, Abeer M. M. Alanazi, Dareen S. S. Mattar, Iman H. H. Hasan
Summary: This study investigated the protective effects of vitamin E and lactobacillus plantarum against mercuric chloride-induced kidney injury. The results showed that both vitamin E and lactobacillus plantarum provided protection against kidney damage by regulating autophagy and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Engineering, Multidisciplinary
Shasha Bai, Sainan Cui, Wenhao Wen, Elaine Lai-Han Leung, Jing Bai, Huiyuan Lin, Yongfei Cui, Lei Yang, Zhongqiu Liu, Yuan Zheng, Rong Zhang
Summary: Tan IIA, an active ingredient of Salvia miltiorrhiza, inhibits lung cancer growth by inducing autophagic apoptosis.
Article
Medicine, Research & Experimental
Man Zhu, Xiaoyu Tang, Zhengyan Gong, Wenjuan Tang, Yanmin Zhang
Summary: This study confirmed the positive correlation between HER2 and EphB4 with E-cadherin in HER2-BC, and inhibition of HER2 or EphB4 can induce apoptosis by decreasing E-cadherin expression. The novel compound TAD shows promising effects on growth inhibition, apoptosis induction, and ROS accumulation in SKBR3 and MDA-MB-453 cells, by blocking both EphB4 and HER2 signal transduction pathways and suppressing E-cadherin/TGF-beta/p-Smad2/3 signaling axis to elicit ROS-dependent endogenous mitochondrial apoptosis.
Article
Obstetrics & Gynecology
Nora Karsten, Thomas Kolben, Sven Mahner, Susanne Beyer, Sarah Meister, Christina Kuhn, Elisa Schmoeckel, Rachel Wuerstlein, Nadia Harbeck, Nina Ditsch, Udo Jeschke, Klaus Friese, Theresa Maria Kolben
Summary: The study revealed that increased E-Cadherin expression in primary tumor tissue of breast cancer patients is associated with poor prognosis, contrary to previous beliefs that loss of E-Cadherin promotes metastasis and invasiveness.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2022)
Article
Biochemistry & Molecular Biology
Lindy J. Pence, Antonis Kourtidis, Ryan W. Feathers, Mary T. Haddad, Sotiris Sotiriou, Paul A. Decker, Aziza Nassar, Idris T. Ocal, Sejal S. Shah, Panos Z. Anastasiadis
Summary: Inflammatory breast cancer expresses high levels of E-cadherin, which promotes tumor metastasis, while the apical adherens junction protein PLEKHA7 is frequently deregulated in this cancer, with re-expression leading to suppression of tumor growth. These findings highlight the potential therapeutic value of targeting the imbalance between apical and basolateral cadherin complexes in inflammatory breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Takako Sakamoto, Keiji Tanimoto, Hidetaka Eguchi, Shunta Sasaki, Kouki Tsuboi, Shin-ichi Hayashi, Sahoko Ichihara
Summary: This study found that resveratrol (RSV) can suppress the metastatic capacity of triple-negative breast cancer (TNBC) and enhance the cytotoxic activity of ABT263 in TNBC cells. Through regulating the expression and histone acetylation levels of CDH1 and CDKN1A, RSV can up-regulate these two genes via epigenetic mechanisms, thereby repressing TNBC metastasis and enhancing the cytotoxic activity of ABT263.
Review
Oncology
Lara Buecker, Ulrich Lehmann
Summary: This article summarizes the research on DNA methylation of the CDH1 gene in human breast cancer and explains the diversity of results. Proper understanding of the methodological basis is crucial for the correct interpretation of the clinical relevance of aberrant DNA methylation in cancer specimens.
Review
Oncology
Xiaoyu Zhu, Xiaoping Wang, Yifei Gong, Junlin Deng
Summary: Thyroid carcinoma is a common and problematic cancer, with recurrence and metastasis being significant issues. Understanding the role of EMT and E-cadherin in tumors is crucial for cancer therapeutics.
CANCER CELL INTERNATIONAL
(2021)
Article
Oncology
Lukasz Lewczuk, Anna Pryczynicz, Katarzyna Guzinska-Ustymowicz
Summary: The study aimed to examine the protein expression levels of E-, N- and P-cadherin in cancer tissue from patients with endometrial cancer and their effects on clinicopathological parameters. Immunohistochemistry revealed uneven distribution of these cadherins in endometrial cancer tissue, with higher expression levels at the tumor front. Additionally, lower membrane expression levels of the 3 cadherin proteins were observed in metastatic cancer cells compared to primary tumor cells.
Article
Cell Biology
Miju Kim, Seav Huong Ly, Yingtian Xie, Gina N. Duronio, Dane Ford-Roshon, Justin H. Hwang, Rita Sulahian, Jonathan P. Rennhack, Jonathan So, Ole Gjoerup, Jessica A. Talamas, Maximilien Grandclaudon, Henry W. Long, John G. Doench, Nilay S. Sethi, Marios Giannakis, William C. Hahn
Summary: Transcriptional co-activator YAP1 is crucial for cell proliferation, survival, and tumorigenesis. This study reveals that the transcription factor PRDM14 can rescue YAP1-dependent colon cancer cells by upregulating the expression of CALM2 and SLC2A1.
DEVELOPMENTAL CELL
(2022)
Article
Biochemistry & Molecular Biology
Nicholas Z. Lue, Emma M. Garcia, Kevin C. Ngan, Ceejay Lee, John G. Doench, Brian B. Liau
Summary: In this study, we use base editing and a DNA methylation reporter to scan mutations of DNMT3A in situ in cells. We identify mutations throughout the protein that disrupt function, including mutations at the interdomain interface that block allosteric activation. Surprisingly, we also find mutations in the PWWP domain that modulate enzyme activity by affecting DNA affinity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hsiao-Yun Chen, Yavuz T. Durmaz, Yixiang Li, Amin H. Sabet, Amir Vajdi, Thomas Denize, Emily Walton, Yasmin Nabil Laimon, John G. Doench, Navin R. Mahadevan, Julie-Aurore Losman, David A. Barbie, Michael Y. Tolstorukov, Charles M. Rudin, Triparna Sen, Sabina Signoretti, Matthew G. Oser
Summary: This study demonstrates that LSD1 inhibition can block the neuroendocrine phenotype of certain small cell lung cancers (SCLCs), and identifies ZFP36L1 as a gene repressed by LSD1 that, when restored, can inhibit SCLC neuroendocrine differentiation. The findings suggest that modulating mRNA stability of lineage transcription factors such as SOX2 and INSM1 can control the neuroendocrine to non-neuroendocrine plasticity in SCLC.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Peter C. DeWeirdt, Abby V. McGee, Fengyi Zheng, Ifunanya Nwolah, Mudra Hegde, John G. Doench
Summary: This study develops a new on-target model that provides optimal predictions for multiple tracrRNA variants and demonstrates significant improvement over previous prediction models on a new dataset. By analyzing the differences in sgRNA activity between tracrRNA variants, the authors identify Pol III transcription termination as a strong determinant of sgRNA activity. These findings are expected to enhance the performance of CRISPR screening and inform future research on tracrRNA engineering and sgRNA modeling.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Kimberly R. Hagel, Rand Arafeh, Sydney Gang, Taylor E. Arnoff, Rebecca C. Larson, John G. Doench, Nathan D. Mathewson, Kai W. Wucherpfennig, Marcela Maus, William C. Hahn
Summary: This study uncovers multiple antigen-dependent and independent mechanisms of CAR T-cell evasion by pancreatic cancer, including the loss of genes involved in GPI-anchor biosynthesis and attachment pathway and genes that regulate tumor transcriptional responses. The identification of these resistance mechanisms provides insights into the landscape of tumor cell intrinsic resistance and potential approaches to improve CAR T-cell therapy efficacy in pancreatic cancer.
Article
Multidisciplinary Sciences
Matteo Gentili, Bingxu Liu, Malvina Papanastasiou, Deborah Dele-Oni, Marc A. Schwartz, Rebecca J. Carlson, Aziz M. Al'Khafaji, Karsten Krug, Adam Brown, John G. Doench, Steven A. Carr, Nir Hacohen
Summary: In this study, genes regulating STING trafficking were systematically characterized, and their impact on STING-mediated responses was examined. The study revealed that the ESCRT complex promotes STING degradation and terminates STING signaling. Furthermore, a UBAP1 mutation was found to increase steady-state STING-dependent responses. Overall, this study uncovers the role of the ESCRT complex in regulating STING signaling.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Kathryn Gunn, Matti Myllykoski, John Z. Cao, Manna Ahmed, Bofu Huang, Betty Rouaisnel, Bill H. Diplass, Michael M. Levitt, Ryan Looper, John G. Doench, Keith L. Ligon, Harley I. Kornblum, Samuel K. McBrayers, Hai Yan, Cihangir Duy, Lucy A. Godley, Peppi Koivunen, Julie-Aurore Losman
Summary: Oncogenic mutations in IDH1 and IDH2 are commonly found in various cancers, including AML and glioma. The mutant IDH enzymes produce (R)-2HG, which is believed to promote cellular transformation by disrupting 2OG-dependent enzymes. This study reveals that (R)-2HG inhibits KDM5 histone lysine demethylases, contributing to cellular transformation in IDH-mutant AML and glioma.
Article
Oncology
Yoshinaga Ito, Deng Pan, Wubing Zhang, Xixi Zhang, Tiffany Y. Juan, Jason W. Pyrdol, Oleksandr Kyrysyuk, John G. Doench, X. Shirley Liu, Kai W. Wucherpfennig
Summary: Tumor heterogeneity is a major obstacle in cancer therapy, including immunotherapy. By targeting autophagy and TNF signaling pathways, MHC-I-deficient tumor cells can be sensitized to T cell-mediated apoptosis. Antigens from apoptotic MHC-I-deficient tumor cells can be efficiently cross-presented by dendritic cells, leading to increased infiltration of T cells producing IFN-γ and TNF-α. Targeting both pathways enables T cell-mediated elimination of tumors with a substantial population of resistant, MHC-I-deficient cells.
Article
Medicine, Research & Experimental
Tianxia Li, Osamu Kikuchi, Jin Zhou, Yichen Wang, Babita Pokharel, Klavdija Bastl, Prafulla Gokhale, Aine Knott, Yanxi Zhang, John G. Doench, Zandra V. Ho, Daniel V. T. Catenacci, Adam J. Bass
Summary: Gastroesophageal adenocarcinomas (GEAs) frequently exhibit amplification of KRAS gene, resulting in overexpression of WT KRAS protein. This study investigates potential targets to enhance the efficacy of SHP2 inhibition in KRAS-amplified GEA, including those within the MAPK pathway and upstream RTKs. In vitro and in vivo experiments demonstrate that pan-ERBB kinase inhibition has potent cytotoxicity. Additionally, the combination of CDK4/6 inhibition with SHP2 inhibition shows greater efficacy in KRAS-amplified GEA compared to KRAS-mutant tumors. These findings suggest potential therapeutic combinations for clinical study in KRAS-amplified GEAs.
Article
Oncology
Baylee A. Porter, Candace Frerich, Muriel Laine, Abigail B. Clark, Ishrat Durdana, Jeon Lee, Manisha Taya, Sunati Sahoo, Geoffrey L. Greene, Lynda Bennett, Suzanne D. Conzen
Summary: The activation of glucocorticoid receptor (GR) inhibits the proliferation of invasive lobular breast cancer (ILC) cells while increasing the risk of metastasis. The expression of GR is associated with the distinctive biology of ILC.
Review
Immunology
Hao Shi, John G. Doench, Hongbo Chi
Summary: CRISPR-based technologies offer a powerful platform for unbiased screening and functional genomics in various fields, including immunology. These technologies have uncovered previously unknown intracellular drivers and intercellular regulators in immune cells, and have expanded the readouts to the transcriptome for better mechanistic insights. CRISPR screens also allow for mapping of genetic interactions to identify genes that synergize or alleviate complex immune phenotypes.
NATURE REVIEWS IMMUNOLOGY
(2023)
Meeting Abstract
Ophthalmology
Karina Luiza Dias Teixeira, Mazhar Adli, John Doench, Gordon W. Laurie
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Oncology
Jessica W. Tsai, Frank P. B. Dubois, Dayle K. Wang, Alexander Crane, Alexandra L. Condurat, Brian Krug, Adam Brown, John G. Doench, Nada Jabado, Pratiti Bandopadhayay
Article
Medicine, Research & Experimental
Patrick C. Lee, Susan Klaeger, Phuong M. Le, Keegan Korthauer, Jingwei Cheng, Varsha Ananthapadmanabhan, Thomas C. Frost, Jonathan D. Stevens, Alan Y. L. Wong, J. Bryan Iorgulescu, Anna Y. Tarren, Vipheaviny A. Chea, Isabel P. Carulli, Camilla K. Lemvigh, Christina B. Pedersen, Ashley K. Gartin, Siranush Sarkizova, Kyle T. Wright, Letitia W. Li, Jason Nomburg, Shuqiang Li, Teddy Huang, Xiaoxi Liu, Lucas Pomerance, Laura M. Doherty, Annie M. Apffel, Luke J. Wallace, Suzanna Rachimi, Kristen D. Felt, Jacquelyn O. Wolff, Elizabeth Witten, Wandi Zhang, Donna Neuberg, William J. Lane, Guanglan Zhang, Lars R. Olsen, Manisha Thakuria, Scott J. Rodig, Karl R. Clauser, Gabriel J. Starrett, John G. Doench, Sara J. Buhrlage, Steven A. Carr, James A. DeCaprio, Catherine J. Wu, Derin B. Keskin
Summary: This study reveals transcriptional suppression of HLA-I antigen presentation in Merkel cell carcinoma and identifies MYCL, PRC1.1, and USP7 as regulators in this process.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Daniel P. Bondeson, Brenton R. Paolella, Adhana Asfaw, Michael Rothberg, Thomas A. Skipper, Carly Langan, Gabriel Mesa, Alfredo Gonzalez, Lauren E. Surface, Kentaro Ito, Mariya Kazachkova, William N. Colgan, Allison Warren, Joshua M. Dempster, John M. Krill-Burger, Maria Ericsson, Andrew A. Tang, Iris Fung, Emily S. Chambers, Mai Abdusamad, Nancy Dumont, John G. Doench, Federica Piccioni, David E. Root, Jesse Boehm, William C. Hahn, Michael Mannstadt, James M. McFarland, Francisca Vazquez, Todd R. Golub
Summary: Despite advances in precision medicine, the clinical prospects for patients with ovarian and uterine cancers remain bleak. In this study, the authors identified a correlation between overexpression of the phosphate importer SLC34A2 and sensitivity to the phosphate exporter XPR1 in cancer cell lines. They also observed this correlation in patient-derived tumor samples. Inhibition of phosphate efflux led to intracellular phosphate accumulation and reduced tumor cell viability.