Article
Multidisciplinary Sciences
Dongsung Kim, Lorenz Herdeis, Dorothea Rudolph, Yulei Zhao, Jark Boettcher, Alberto Vides, Carlos I. I. Ayala-Santos, Yasin Pourfarjam, Antonio Cuevas-Navarro, Jenny Y. Xue, Andreas Mantoulidis, Joachim Broeker, Tobias Wunberg, Otmar Schaaf, Johannes Popow, Bernhard Wolkerstorfer, Katrin Gabriele Kropatsch, Rui Qu, Elisa de Stanchina, Ben Sang, Chuanchuan Li, Darryl B. B. McConnell, Norbert Kraut, Piro Lito
Summary: This study reports the discovery of a non-covalent inhibitor that selectively binds to the inactive state of KRAS while sparing other RAS isoforms. The inhibitor blocks nucleotide exchange and inhibits the activation of wild-type and various KRAS mutants. It shows promising therapeutic potential for KRAS-driven cancers.
Article
Biochemistry & Molecular Biology
Nada Ragab, Julia Bauer, Dominik S. Botermann, Anja Uhmann, Heidi Hahn
Summary: The study shows that oncNRAS mutations accelerate tumor growth in immature ERMS precursors within a specific time window, shortening ERMS-free survival and increasing ERMS incidence. However, it does not alter tumor differentiation and is not involved in tumor initiation. This indicates that oncNRAS-associated processes differ in dependency on their occurrence during tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Beryl L. Manning-Geist, Sonia Gatius, Ying Liu, Mabel Gil, Arnaud Da Cruz Paula, Noemi Tuset, Nadeem R. Abu-Rustum, Carol Aghajanian, Britta Weigelt, Xavier Matias-Guiu
Summary: The article presents a rare case of Cowden syndrome-associated endometrial carcinoma, discussing the clinical, pathological, and molecular features of the tumor, as well as predisposing inherited syndromes to endometrial carcinoma and PTEN-targeted therapies.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Pathology
Moonsik Kim, Jinhee Kim, An Na Seo, Ji Yun Jeong, Nora Jee-Young Park, Gun Oh Chong, Dae Gy Hong, Ji Young Park
Summary: This study provides a detailed analysis of the immunostaining pattern of oncogenic PTEN missense mutations and suggests that complementary testing using both immunostaining and next-generation sequencing is necessary to accurately evaluate the PTEN status in malignancy.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Cell Biology
Imran Khan, Akiko Koide, Mariyam Zuberi, Gayatri Ketavarapu, Eric Denbaum, Kai Wen Teng, J. Matthew Rhett, Russell Spencer-Smith, G. Aaron Hobbs, Ernest Ramsay Camp, Shohei Koide, John P. O'Bryan
Summary: This study discovered a compound that selectively binds to the nucleotide-free state of RAS and inhibits the signaling and transforming activity of certain RAS mutants with fast exchange rates. In cell experiments and animal models, this compound exhibited the ability to reduce tumor formation in cancer cells.
Article
Oncology
Dantong Zhu, Fengtong Han, Liuke Sun, Sandeep K. Agnihotri, Ying Hu, Hansruedi Bueeler
Summary: Mitochondrial metabolism and dynamics play a critical role in the growth of Ras-dependent tumor cells, and loss of PINK1 inhibits tumor growth by affecting mitochondrial fission and associated cell necrosis and cell cycle defects.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pathology
Cindy Wepy, David B. Chapel, George L. Mutter, Bradley J. Quade, Marisa R. Nucci, Carlos Parra-Herran
Summary: Gestational endometrium can exhibit various atypical but benign changes, and one such lesion is localized endometrial proliferation of pregnancy (LEPP). To understand its significance, the pathologic, immuno-phenotypic, and molecular features of LEPP were investigated. Nine cases of LEPP were reviewed, and immunohistochemistry and next-generation sequencing were performed. LEPP features intraglandular cribriform/solid architecture, positive estrogen receptor/progesterone receptor, PTEN loss, and PIK3CA and PTEN mutations. LEPP should be distinguished from other endometrial neoplasms due to its unique clinicopathologic context and indolent outcome.
Article
Medicine, Research & Experimental
Linlin Yang, Zhefeng Li, Daniel W. Binzel, Peixuan Guo, Terence M. Williams
Summary: This study suggests that nanoparticles targeting mutant KRAS can effectively suppress cancer cell proliferation and migration, and enhance sensitivity to chemoradiotherapy in lung cancer. These findings highlight the potential of this nanoparticle-based platform as a novel treatment strategy for KRAS-driven human cancers.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Multidisciplinary Sciences
Alfredo Erazo-Oliveras, Monica Munoz-Vega, Mohamed Mlih, Venkataramana Thiriveedi, Michael L. Salinas, Jaileen M. Rivera-Rodriguez, Eunjoo Kim, Rachel C. Wright, Xiaoli Wang, Kerstin K. Landrock, Jennifer S. Goldsby, Destiny A. Mullens, Jatin Roper, Jason Karpac, Robert S. Chapkin
Summary: This study reveals the role of mutant APC in colorectal cancer by disrupting plasma membrane sterol homeostasis and modulating Wnt signaling hubs. It has been found that Wnt signaling originates from dynamic nano-assemblies at the plasma membrane. The oncogenic APC increases plasma membrane free cholesterol and rigidity, leading to overactivation of Wnt signaling in the colon. Exogenous free cholesterol can disrupt plasma membrane homeostasis and drive Wnt signaling in wildtype APC background. These findings provide a link between oncogenic APC, loss of plasma membrane homeostasis, and CRC development.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Yoshiaki Maru, Naotake Tanaka, Yasutoshi Tatsumi, Yuki Nakamura, Makiko Itami, Yoshitaka Hippo
Summary: KRAS, an oncogene frequently activated by mutations, plays a key role in adenocarcinoma development in various organs. Activation of Kras in endometrial cells could lead to the development of sarcoma, with potential context-dependent variations in oncogenic potential and tumor histological features.
Article
Biochemistry & Molecular Biology
Linlin Yang, Changxian Shen, Adriana Estrada-Bernal, Ryan Robb, Moumita Chatterjee, Nikhil Sebastian, Amy Webb, Xiaokui Mo, Wei Chen, Sunil Krishnan, Terence M. Williams
Summary: This study found that KRAS mutations lead to radioresistance by activating the NRF2-53BP1 axis in DNA repair and tumor cell survival after radiotherapy. Targeting NRF2, 53BP1, or NHEJ may represent novel strategies to selectively abrogate KRAS mutation-mediated radioresistance.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Pathology
Xiyin Wang, Mariana S. L. Praca, Jillian R. H. Wendel, Robert E. Emerson, Francesco J. DeMayo, John P. Lydon, Shannon M. Hawkins
Summary: Oncogenic KRAS mutations and loss-of-function mutations in the ARID1A gene are common in endometrial cancers. However, a study on mutant mice suggests that the combined effects of these genetic insults can lead to invasive vaginal squamous cell carcinoma.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Cell & Tissue Engineering
Siyu Xia, Ming Wu, Xinhao Zhou, Xiu Zhang, Lina Ye, Kang Zhang, Yiyi Kang, Jun Liu, Yunci Zhang, Wang Wu, Dirong Dong, Hong Chen, Hui Li
Summary: Conditionally reprogrammed physiological endometrial epithelial cells provide a novel therapeutic strategy for IUA by repairing the injured endometrium and improving pregnancy rate.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Medicine, Research & Experimental
Kanchan Singh, Melissa Pruski, Rachael Bland, Mamoun Younes, Sushovan Guha, Nirav Thosani, Anirban Maitra, Brooks D. Cash, Florencia McAllister, Craig D. Logsdon, Jeffrey T. Chang, Jennifer M. Bailey-Lundberg
Summary: The study found that ectopic expression of oncogenic mutant K-Ras in pancreatic ducts generates early and late PanIN as well as PDAC, with evidence suggesting that AKT signaling is an important early driver of invasive ductal derived PDAC. This Ras rheostat model highlights the significance of elevated Kras mutation frequency and loss of PTEN in driving PanIN and invasive ductal derived PDAC.
LABORATORY INVESTIGATION
(2021)
Article
Biology
Yong-Li Dong, Gangadhara P. Vadla, Jin-Yu (Jim) Lu, Vakil Ahmad, Thomas J. Klein, Lu-Fang Liu, Peter M. Glazer, Tian Xu, Chiswili-Yves Chabu
Summary: Oncogenic RAS mutations lead to tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment are crucial for therapy outcomes. Blocking cell-cell communication loops can resensitize Ras tumor cells to irradiation.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Maria M. Szwarc, Ramakrishna Kommagani, Vasanta Putluri, Julien Dubrulle, Fabio Stossi, Michael A. Mancini, Cristian Coarfa, Rainer B. Lanz, Nagireddy Putluri, Francesco J. DeMayo, John P. Lydon, Bert W. O'Malley
SCIENTIFIC REPORTS
(2018)
Article
Multidisciplinary Sciences
Hong Zhao, Ling Zhou, Lin Li, John Coon, Robert T. Chatterton, David C. Brooks, Enze Jiang, Li Liu, Xia Xu, Zhiyong Dong, Francesco J. DeMayo, Jonah J. Stulberg, Warren G. Tourtellotte, Serdar E. Bulun
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Endocrinology & Metabolism
Ru-pin Alicia Chi, Tianyuan Wang, Nyssa Adams, San-pin Wu, Steven L. Young, Thomas E. Spencer, Francesco DeMayo
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2020)
Article
Endocrinology & Metabolism
Gerardo G. B. Herrera, Sydney L. Lierz, Emily A. Harris, Lauren J. Donoghue, Sylvia C. Hewitt, Karina F. Rodriguez, Wendy N. Jefferson, John P. Lydon, Francesco J. DeMayo, Carmen J. Williams, Kenneth S. Korach, Wipawee Winuthayanon
Article
Medicine, Research & Experimental
Ru-pin Alicia Chi, Tianyuan Wang, Chou-Long Huang, San-pin Wu, Steven L. Young, John P. Lydon, Francesco J. DeMayo
Article
Multidisciplinary Sciences
Olga Kim, Eun Young Park, Sun Young Kwon, Sojin Shin, Robert E. Emerson, Yong-Hyun Shin, Francesco J. DeMayo, John P. Lydon, Donna M. Coffey, Shannon M. Hawkins, Lawrence A. Quilliam, Dong-Joo Cheon, Facundo M. Fernandez, Kenneth P. Nephew, Adam R. Karpf, Martin Widschwendter, Anil K. Sood, Robert C. Bast, Andrew K. Godwin, Kathy D. Miller, Chi-Heum Cho, Jaeyeon Kim
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Endocrinology & Metabolism
Leah Hawkins Bressler, Marc A. Fritz, San-Pin Wu, Lingwen Yuan, Suzanna Kafer, Tianyuan Wang, Francesco J. DeMayo, Steven L. Young
Summary: The study found reduced proliferation and angiogenesis markers, increased inflammation, and altered ER expression patterns in women with suboptimal endometrial thickening after clomiphene treatment. The results suggest potential mechanisms underlying the lower pregnancy rates associated with suboptimal endometrial thickening in these women.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Multidisciplinary Sciences
Andrew M. Kelleher, Rohit Setlem, Francoise Dantzer, Francesco J. DeMayo, John P. Lydon, W. Lee Kraus
Summary: This study found that catalytic inhibition or genetic ablation of PARP-1 and PARP-2 in the uterus led to pregnancy loss in mice, associated with increased p53 signaling and an increased population of senescent decidual cells, with decidualization failure being the cause of pregnancy loss.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Developmental Biology
Manoj K. Madhavan, Francesco J. DeMayo, John P. Lydon, Niraj R. Joshi, Asgerally T. Fazleabas, Ripla Arora
Summary: The uterine luminal epithelium folds characteristically in mammals, including humans, horses and rodents. However, the precise function of these folds remains unknown. This study reveals dynamic changes in the 3D uterine folding pattern during early pregnancy and suggests that the folds and chambers are two distinct structures with specific roles in implantation and post-implantation morphogenesis.
Article
Developmental Biology
Mackenzie J. Dickson, Yeong Seok Oh, Artiom Gruzdev, Rong Li, Nuria Balaguer, Andrew M. Kelleher, Thomas E. Spencer, San-Pin Wu, Francesco J. DeMayo
Summary: Approximately 75% of unsuccessful pregnancies are caused by implantation failure. This study developed a mouse strain with a decidual-specific iCre recombinase and confirmed its activity and tissue specificity during pregnancy. This research provides a valuable tool for investigating genetic networks and cellular dynamics associated with decidualization and infertility.
Article
Endocrinology & Metabolism
Sylvia C. Hewitt, San-pin Wu, Tianyuan Wang, Madhumita Ray, Marja Brolinson, Steven L. Young, Thomas E. Spencer, Alan DeCherney, Francesco J. DeMayo
Summary: This study investigates the molecular processes underlying estrogen responses and their effects on endometrial health. By analyzing the ESR1 cistromes and transcriptomes of endometrial biopsies and organoids, the study identifies candidate ESR1 target genes and reveals differences in the distribution and regulation of ESR1 binding sites between different stages of the menstrual cycle. The findings provide valuable resources for understanding how estrogen affects endometrial function and health.
Article
Biochemistry & Molecular Biology
Sylvia C. Hewitt, Artiom Gruzdev, Cynthia J. Willson, San-Pin Wu, John P. Lydon, Niels Galjart, Francesco J. DeMayo
Summary: Receptors for estrogen and progesterone interact via Cohesin/CTCF loop extrusion at enhancers distal from regulated genes. Loss-of- function CTCF mutation indicates its importance in uterine homeostasis. Deleting Ctcf gene in female reproductive tissues of mice resulted in reduced uterine glands and hypoplastic uteri with decreased endometrial stroma. Ctcf deletion also altered the expression of progesterone-responsive genes, including Ihh, Fst, and Errfi1. Our findings highlight the key role of uterine Ctcf in progesterone-dependent expression and optimal post-pubertal uterine development.
Article
Multidisciplinary Sciences
Rong Li, Tianyuan Wang, Ryan M. Marquardt, John P. Lydon, San-Pin Wu, Francesco J. DeMayo
Summary: Estrogen and progesterone regulate uterine biology through their receptors ERα and PR, respectively. This study identifies TRIM28 as a protein that interacts with ERα and PR to regulate uterine function. TRIM28 deficiency disrupts PR and ERα chromatin binding, resulting in the inability of the uterus to support early pregnancy.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Sylvia C. Hewitt, Artiom Gruzdev, Cynthia J. Willson, San-Pin Wu, John P. Lydon, Niels Galjart, Francesco J. DeMayo
Summary: Receptors for estrogen and progesterone interact through Cohesin/CTCF loop extrusion at enhancers distal from regulated genes. Loss-of-function CTCF mutation in endometrial tumors indicates its importance in uterine homeostasis. Our study reveals that uterine Ctcf plays a key role in progesterone-dependent expression of uterine genes underlying optimal post-pubertal uterine development.
Article
Multidisciplinary Sciences
San-Pin Wu, Tianyuan Wang, Zheng-Chen Yao, Mary C. Peavey, Xilong Li, Lecong Zhou, Irina V. Larina, Francesco J. DeMayo
Summary: PGR plays a pivotal role in directing the molecular program for uterine remodeling and pregnancy support. Mutant PGR can lead to dysfunction of the myometrium, affecting fertility and pregnancy adaptation.