Article
Medicine, General & Internal
Maria Lourdes Garza-Rodriguez, Victor Trevino, Antonio Ali Perez-Maya, Hazyadee Frecia Rodriguez-Gutierrez, Moises Gonzalez-Escamilla, Miguel Angel Elizondo-Riojas, Genaro A. Ramirez-Correa, Oscar Vidal-Gutierrez, Carlos Horacio Burciaga-Flores, Diana Cristina Perez-Ibave
Summary: In this study, a novel pathogenic germline variant in the APC gene was identified using NGS. The variant was confirmed in multiple family members and associated with atypical clinical symptoms. This variant is classified as a PVS1 variant according to ACMG guidelines, providing evidence for early surveillance and suitable treatment in patients with the variant.
Article
Cell Biology
Shumei Chia, Thomas Leung, Ivan Tan
Summary: LRAP35a plays a crucial role in cell migration by coordinating lamellar contractility and microtubule polarization for efficient directional movement. Its regulation of actomyosin and microtubule networks is tightly controlled by a series of phosphorylation events, influencing the interaction and dissociation of key proteins involved in cellular movement.
Article
Oncology
Misato Takao, Tatsuro Yamaguchi, Hidetaka Eguchi, Takeshi Yamada, Yasushi Okazaki, Naohiro Tomita, Tadashi Nomizu, Tomoyuki Momma, Tetsuji Takayama, Kohji Tanakaya, Kiwamu Akagi, Hideyuki Ishida
Summary: Familial adenomatous polyposis (FAP) is a rare genetic disorder caused by a pathogenic variant of the APC gene, but this variant is not detected in up to 30% of patients with the adenomatous polyposis phenotype. Next-generation sequencing (NGS) was used to identify causative genes in FAP patients with 10 or more polyps, and APC mosaicism was detected in nine patients. The study found that APC germline variants were associated with specific phenotypes and increasing numbers of extracolonic lesions.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Junxiu Nong, Kexin Kang, Qiaoni Shi, Xuechen Zhu, Qinghua Tao, Ye-Guang Chen
Summary: The liquid-liquid phase separation of Axin drives the formation of the destruction complex, facilitating the recruitment of other members and promoting phosphorylation of beta-catenin, critical for regulating Wnt/beta-catenin signaling.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Immunology
Celine Cuche, Marta Mastrogiovanni, Marie Juzans, Helene Laude, Marie-Noelle Ungeheuer, Daniel Krentzel, Maria Isabella Gariboldi, Daniel Scott-Algara, Marianne Madec, Sophie Goyard, Camille Floch, Gaelle Chauveau-Le Friec, Pierre Lafaye, Charlotte Renaudat, Muriel Le Bidan, Christine Micallef, Sandrine Schmutz, Sebastien Mella, Sophie Novault, Milena Hasan, Darragh Duffy, Vincenzo Di Bartolo, Andres Alcover
Summary: Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of colorectal adenomas with high risk of becoming colorectal tumors. Mutations of the Adenomatous polyposis coli (APC) gene are often responsible for FAP. Our recent study suggests that the APC protein is involved in multiple phases of T cell responses. We investigated immune cell abnormalities in FAP subjects and found dysfunctions in various immune cell populations, gene expressions, cytokine and chemokine productions, and T cell migration.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Chenchen Li, Emma E. Furth, Anil K. Rustgi, Peter S. Klein
Summary: The Wnt signaling pathway is crucial in metazoan development and stem cell maintenance, and is also involved in various malignancies. Apart from the canonical activation, the pathway can affect cell function through multiple alternative effectors, potentially contributing to cancer development.
Article
Medical Laboratory Technology
Faranak Ghadamyari, Mohammad Mehdi Heidari, Sirous Zeinali, Mehri Khatami, Shahin Merat, Hamideh Bagherian, Leili Rejali, Farzaneh Ghasemi
Summary: This study conducted genetic screening of 59 FAP Iranian patients in 10 families to investigate APC gene mutations in FAP tumorigenesis. A total of 12 germline heterozygous and homozygous nucleotide variations were identified, including two missense mutations, four nonsense mutations, four synonymous variations, and two nucleotide deletions. The findings suggest potential biomarkers and provide insights into the role of the APC gene in FAP.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2021)
Review
Biochemistry & Molecular Biology
Ilaria Ditonno, Domenico Novielli, Francesca Celiberto, Salvatore Rizzi, Maria Rendina, Enzo Ierardi, Alfredo Di Leo, Giuseppe Losurdo
Summary: Familial adenomatous polyposis (FAP) is a genetic syndrome characterized by the presence of multiple polyps in the gastrointestinal tract and various systemic extra-intestinal manifestations. The pathogenesis of FAP is associated with a loss of function mutation in the adenomatous polyposis coli (APC) gene and involves multiple mechanisms such as gut microbiota composition, immune microenvironment, inflammation, estrogen, and signaling pathways. Understanding these pathways can help develop targeted therapies and chemopreventive strategies to improve the quality of life for individuals and families affected by FAP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Rachel Schwiter, Heather Rocha, Alicia Johns, Juliann M. Savatt, David L. Diehl, Melissa A. Kelly, Marc S. Williams, Adam H. Buchanan
Summary: This study describes the clinical presentation of individuals with APC P/LP variants causative of familial adenomatous polyposis in an unselected health care system cohort. The prevalence of APC P/LP variants in this cohort is estimated to be higher than previously published rates. Individuals identified via genomic screening had a low adenoma burden compared to controls.
GENETICS IN MEDICINE
(2023)
Article
Cell Biology
Xingyuan Fang, Tatyana M. Svitkina
Summary: The APC protein, known for its role as a tumor suppressor and in Wnt signaling regulation, also plays a crucial role in cell migration as a cytoskeletal protein. Mutations in the APC gene are associated with colorectal cancer and neurological disorders. Understanding how APC regulates cell motility is still incomplete, but recent research suggests its involvement in initiating leading edge protrusion through interactions with microtubules and the Arp2/3 complex.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2022)
Article
Genetics & Heredity
Worrawit Wanitsuwan, Sukanya Vijasika, Pichai Jirarattanasopa, Sukanya Horpaopan
Summary: A novel pathogenic variant in the APC gene was identified in Southern Thai FAP patients, leading to skipping of exon 10. Segregation study confirmed its inheritance pattern in affected family members across three generations. The phenotypic spectrum varied within the family, with some members exhibiting extracolonic manifestations.
BMC MEDICAL GENOMICS
(2021)
Article
Genetics & Heredity
Vittoria Disciglio, Giovanna Forte, Candida Fasano, Paola Sanese, Martina Lepore Signorile, Katia De Marco, Valentina Grossi, Filomena Cariola, Cristiano Simone
Summary: Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC, most of which result in truncated protein products. A study found 119 unique APC splicing mutations reported in FAP patients, with some leading to exon skipping associated with the attenuated FAP (AFAP) phenotype.
Article
Pathology
Tomoaki Naka, Taiki Hashimoto, Hourin Cho, Noriko Tanabe, Teruhiko Yoshida, Yasushi Yatabe, Takaki Yoshikawa, Seiichiro Abe, Shigeki Sekine
Summary: Gastric foveolar-type adenoma (FA) is a rare benign neoplasm that can either occur sporadically or in patients with familial adenomatous polyposis (FAP). This study aimed to investigate the molecular features of FA and the relationship between sporadic and syndromic lesions. The results showed that sporadic FA includes at least two morphologically and genetically distinct subtypes: flat and raspberry-like FA. Additionally, it was found that flat FA represents a sporadic counterpart of FAP-associated FA.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Article
Oncology
Miaorong Xu, Yuyan Zheng, Zhongchao Zuo, Qin Zhou, Qun Deng, Jianwei Wang, Da Wang
Summary: This case report presents a 20-year-old female with familial adenomatous polyposis (FAP) who initially presented with thyroid cancer and later developed colon cancer liver metastases. Genetic testing revealed a novel mutation in the APC gene. The mutation may contribute to the pathogenesis of the disease through beta-catenin accumulation, cell cycle microtubule dysregulation, and tumor suppressor inactivation.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Wei Huang, Jin Bian, Xiaoping Qian, Lin Shao, Haiyan Li, Lu Zhang, Lin Wang
Summary: This study presented a case of a 20-year-old CRC patient with mutations in both APC and BRCA1 genes, along with a history of colorectal and other cancers in the family. The first ever coexistence of APC and BRCA1 mutations was identified through genetic analysis, shedding light on the inheritance patterns within the family. This case highlights the importance of evaluating detailed family history and conducting multiple-gene panel testing in patients with hereditary cancer.
FRONTIERS IN ONCOLOGY
(2021)
Review
Cell Biology
Sarannya Edamana, Frederic H. Login, Soichiro Yamada, Tae-Hwan Kwon, Lene N. Nejsum
Summary: Aquaporins (AQPs) are proteins that facilitate passive transport of water across cellular membranes, playing important roles in physiology such as regulation of body water homeostasis, skin hydration, and fat metabolism. Dysregulation of AQPs is associated with various pathophysiological conditions and major players in multiple cancers, influencing cellular signaling, migration, proliferation, and regulation of junctional proteins involved in cell-cell adhesion.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Physiology
Jean-Claude Kresse, Henricus A. M. Mutsaers, Michael Schou Jensen, Stine Julie Tingskov, Mia Gebauer Madsen, Lene N. Nejsum, Helle Praetorius, Rikke Norregaard
Summary: This study evaluated the role of the PGE(2)-EP1 receptor in renal fibrosis and found that EP1 receptor inhibition can attenuate fibrogenesis, suggesting it as a promising therapeutic target.
Article
Physiology
Christina Ernstsen, Frederic H. Login, Anne-Sofie B. Schelde, Jacob R. Therkildsen, Jakob Moller-Jensen, Rikke Norregaard, Helle Praetorius, Lene N. Nejsum
Summary: This study found that the urinary concentration defect in patients with acute pyelonephritis may be related to abnormal cellular localization of AQP2. Pathogenic bacteria can induce membrane targeting of AQP2, and this effect does not depend on an increase in cAMP levels or phosphorylation of the S256 site.
Review
Immunology
Malte Bystrup, Frederic H. Login, Sarannya Edamana, Signe Borgquist, Trine Tramm, Tae-Hwan Kwon, Lene N. Nejsum
Summary: Aquaporin-5 (AQP5) is essential in transepithelial water transport and its ectopic overexpression in breast cancer is associated with lymph node metastasis and poor prognosis. In addition to its role in water transport, AQP5 also plays a role in cancer metastasis, migration, and proliferation. Understanding the molecular mechanisms of AQP5 in cancer development and progression is crucial for its potential use as a prognostic biomarker and for the development of targeted interventions for breast cancer treatment.
Review
Immunology
Laura Traberg-Nyborg, Frederic H. Login, Sarannya Edamana, Trine Tramm, Signe Borgquist, Lene N. Nejsum
Summary: The overexpression of aquaporin in breast cancer is associated with poor prognosis and affects cellular processes like migration, angiogenesis, and proliferation, providing potential mechanisms for the progression and metastasis of breast cancer.
Article
Cell Biology
Sarannya Edamana, Frederic H. Login, Andreas Riishede, Vibeke S. Dam, Trine Tramm, Lene N. Nejsum
Summary: Breast carcinomas are associated with increased cell proliferation, migration, altered cellular adhesion, and loss of epithelial polarity. Aquaporin-5 (AQP5) is aberrantly expressed in breast cancer and is linked to metastasis and poor prognosis. AQP5 enhances cancer cell proliferation and migration, reduces cell-cell adhesion, and activates the Ras pathway. This study explores the relationship between AQP5 and the polarity protein Scribble. Results show that high AQP5 expression is inversely related to Scribble levels in breast carcinoma tissue samples. Overexpression of AQP5 in breast cancer cells reduces spheroid size, circularity, and Scribble levels. The effect of AQP5 on Scribble is partially dependent on AQP5-mediated activation of Ras. These findings suggest that AQP5 negatively regulates cellular polarity in breast cancer.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sarannya Edamana, Stine F. Pedersen, Lene N. Nejsum
Summary: Aquaporin (AQP) water channels play a crucial role in the transport of water across cellular membranes and are associated with breast cancer. In vitro studies have shown that AQPs can influence the effectiveness of conventional anticancer chemotherapies. This study focused on AQP1, AQP3, and AQP5, which are often overexpressed in breast cancer, and evaluated their impact on the viability of breast cancer cell spheroids treated with different chemotherapies. The findings support the significant role of AQPs in the response to conventional chemotherapies and highlight the importance of understanding the individual proteins involved in resistance to chemotherapy for personalized medicine in breast cancer.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Christina V. Ernstsen, Andreas Riishede, Anne Kristine S. Iversen, Lene Bay, Thomas Bjarnsholt, Lene N. Nejsum
Summary: Chronic wounds are a significant burden on society and are estimated to affect 1-2% of the global population. The expression of E-cadherin and aquaporin-3, important for skin function and cell migration, is found to be low at the edges of chronic wounds according to immunohistochemical stainings. Further studies are needed to understand the association between this downregulation and the pathophysiology of chronic wounds.
Article
Immunology
Soren H. Elsborg, Gitte A. Pedersen, Mia G. Madsen, Anna K. Keller, Rikke Norregaard, Lene N. Nejsum
Summary: Animal and human tissues are commonly used in physiological and pathophysiological research. A new method has been developed to allow for multiplex immunofluorescence staining of kidney sections in order to reuse the same tissue section multiple times, which addresses both ethical concerns and limited availability.
Article
Neurosciences
Maria Venneri, Vanessa Vezzi, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Grazia Tamma, Lene N. Nejsum, Giovanna Valenti
Summary: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease caused by gain-of-function mutations of arginine vasopressin receptor 2 (V2R). The constitutive AQP2 trafficking associated with the gain-of-function V2R-R137L/C mutants causing NSIAD is protein kinase A independent and requires an intact Ser269 in AQP2 under the control of ROCK phosphorylation.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Cell Biology
Stine Julie Tingskov, Mariagrazia D'Agostino, Frederic H. Login, Grazia Tamma, Lene N. Nejsum, Rikke Norregaard
Summary: In this study, the effect of tamoxifen (TAM) on the expression and localization of aquaporin 3 (AQP3) in collecting ducts was investigated. TAM attenuated the downregulation of AQP3 in a unilateral ureteral obstruction (UUO) model and a lithium-induced nephrogenic diabetes insipidus (NDI) model, and affected the intracellular localization in the collecting ducts. TAM also influenced the expression profile of other basolateral proteins.
Article
Biochemistry & Molecular Biology
Antoni Kowalski, Cristine Betzer, Sigrid Thirup Larsen, Emil Gregersen, Estella A. Newcombe, Montana Caballero Bermejo, Viktor Wisniewski Bendtsen, Jorin Diemer, Christina Ernstsen, Shweta Jain, Alicia Espina Bou, Annette Eva Langkilde, Lene N. Nejsum, Edda Klipp, Robert Edwards, Birthe B. Kragelund, Poul Henning Jensen, Poul Nissen
Summary: This study shows that monomeric alpha-synuclein can activate plasma membrane Ca2+-ATPase (PMCA) to promote calcium clearance in neurons. The colocalization of alpha-synuclein and PMCA at neuronal synapses suggests a potential physiological function for alpha-synuclein in regulating calcium expulsion.
Review
Urology & Nephrology
Frederic H. Login, Lene N. Nejsum
Summary: Aquaporins play a crucial role in renal water handling and body water homeostasis. They are also involved in water reabsorption and secretion in other tissues, transport of small molecules and gases, and various cellular processes. Furthermore, the expression of certain AQPs is related to cancer progression and drug response, suggesting their potential application in prognostics and therapeutics.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Cell Biology
Pernille Bogetofte Thomasen, Alena Salasova, Kasper Kjaer-Sorensen, Lucie Woloszczukova, Josef Lavicky, Hande Login, Jeppe Tranberg-Jensen, Sergio Almeida, Sander Beel, Michaela Kavkova, Per Qvist, Mads Kjolby, Peter Lund Ovesen, Stella Nolte, Benedicte Vestergaard, Andreea-Cornelia Udrea, Lene Niemann Nejsum, Moses Chao, Philip Van Damme, Jan Krivanek, Jeremy Dasen, Claus Oxvig, Anders Nykjaer
Summary: SorCS2 is a receptor for PGRN that plays an important role in MN diversification and axon outgrowth, as well as affecting neuromuscular junction morphology and fish motility. Deficiency of SorCS2 disrupts cell-fate decisions of brachial MNs and leads to innervation deficits of posterior nerves. In addition, SorCS2 knockout mice exhibit slower motor nerve regeneration. The interaction between primitive macrophages expressing high levels of PGRN and SorCS2-positive motor axons is crucial for axon pathfinding.
Article
Cell Biology
Teresa Kirkegaard, Andreas Riishede, Trine Tramm, Lene N. Nejsum
Summary: Aquaporins are water channels that facilitate passive water transport across cellular membranes. Some aquaporins, such as AQP1, AQP3 and AQP5, are overexpressed in breast cancer and associated with poor prognosis. The aquaglyceroporins AQP3, AQP7, and AQP9 are expressed in human breast cancer and may be potential targets for intervention strategies aiming at cellular metabolism.
