Review
Cell Biology
Ian James Bell, Matthew Sheldon Horn, Terence John Van Raay
Summary: The non-canonical Wnt signaling pathways have different roles in cancer and development, involving calcium and Vangl2. Cells tend to choose non-canonical Wnt signaling over canonical Wnt signaling when presented with a choice, but this occurs rarely in vivo.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Engineering, Biomedical
Derek Avery, Lais Morandini, Luke S. Sheakley, Arth H. Shah, Loc Bui, Jefferson O. Abaricia, Rene Olivares-Navarrete
Summary: This study investigates the role of canonical Wnt signaling in the response of macrophages to titanium surface properties. The results show that activating canonical Wnt signaling promotes a pro-inflammatory phenotype, while inhibiting it enhances an anti-inflammatory response.
Review
Biochemistry & Molecular Biology
Silvia Muccioli, Valentina Brillo, Leonardo Chieregato, Luigi Leanza, Vanessa Checchetto, Roberto Costa
Summary: The Wnt signaling pathway is crucial in embryonic development for controlling cell proliferation, but aberrant activation in human diseases has been observed. Ion channels, known as modulators of important cellular functions, have been widely researched for their influence on Wnt signaling regulation. This review focuses on the links between ion channels and canonical Wnt signaling, discussing their potential roles in human metabolic diseases, neurological disorders, and cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Lauren V. Albrecht, Nydia Tejeda-Munoz, Edward M. De Robertis
Summary: Recent investigations have revealed that Wnt signaling can regulate various cell physiological effects, promoting cell growth by mechanisms such as Wnt receptor endocytosis, Wnt-induced protein stabilization, and metabolic changes. A key element is the sequestration of glycogen synthase kinase 3 (GSK3) inside multivesicular bodies and lysosomes, which affects the phosphorylation motifs of GSK3 and protein degradation. These effects are independent of new protein synthesis and contribute to cell growth.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 37
(2021)
Article
Multidisciplinary Sciences
Ana R. Moshkovsky, Marc W. Kirschner
Summary: Axin is a crucial protein in the canonical Wnt pathway, and its differential regulation allows for tissue-specific functions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Jose A. Gomez, Alan Payne, Richard E. Pratt, Conrad P. Hodgkinson, Victor J. Dzau
Summary: The study demonstrates the importance of Sfrp2 in promoting cardiomyogenesis in vivo by switching the fate of multipotent cKit(+) cells to differentiate solely into cardiomyocytes, leading to significant functional improvements in a cardiac injury model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Developmental Biology
Eva Janeckova, Jifan Feng, Tingwei Guo, Xia Han, Aileen Ghobadi, Angelita Araujo-Villalba, Md Shaifur Rahman, Heliya Ziaei, Thach-Vu Ho, Siddhika Pareek, Jasmine Alvarez, Yang Chai
Summary: This study reveals the crucial role of Wnt signaling in soft palate development and muscle differentiation through the regulation of ciliary homeostasis. Wnt signaling activates ciliary gene Ttll3 expression, which is necessary for mesenchymal cell proliferation and subsequent myogenesis.
Article
Ophthalmology
Zhen Liu, Yanghui Xiu, Fangfang Qiu, Zhenzhen Zhu, Rongrong Zong, Xiangtian Zhou, Jianhong An, Qiongsi Wang, Peter S. Reinach, Wei Li, Wensheng Chen, Zuguo Liu
Summary: This study found that plasma levels of Wnt inhibitor DKK-1 were significantly reduced in patients with myopia, while the canonical Wnt pathway was progressively activated during myopia development in mice. Targeting Wnt signaling pathways has the potential to be a therapeutic strategy for myopia by inhibiting myopia progression.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Vishnu V. Krishnamurthy, Hyojeong Hwang, Jia Fu, Jing Yang, Kai Zhang
Summary: Optogenetics utilizes light-inducible protein-protein interactions to control signaling activity with precision, offering attractive spatial and temporal resolution for studying embryonic development. In a comparative study, a cytoplasm-to-membrane translocation-based optogenetic system outperformed membrane-anchored dimerization systems in activating receptor tyrosine kinase signaling in live Xenopus embryos. This engineering strategy may have broad applicability to other signaling pathways involving membrane-bound receptors, as demonstrated by triggering Wnt activity through optogenetic activation of LRP6.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Mei Yang, Lin Li, Xiaojie Huang, Hui Xing, Li Hong, Chunfan Jiang
Summary: Abnormal methylation of the SFRP2 gene plays a crucial role in the development of endometriosis. SFRP2 is demethylated and upregulated in ectopic endometrium and epithelial cells, leading to increased activation of the Wnt/β-catenin signaling pathway and enhanced invasion and migration ability.
BMC MOLECULAR AND CELL BIOLOGY
(2023)
Article
Orthopedics
Frank C. Ko, Meghan M. Moran, Ryan D. Ross, D. Rick Sumner
Summary: The study found that the activation of canonical Wnt signaling can accelerate intramembranous bone regeneration in male mice but has no effect on female mice.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Article
Peripheral Vascular Disease
Irena Kasacka, Zaneta Piotrowska, Natalia Domian, Magdalena Acewicz, Alicja Lewandowska
Summary: The study revealed alterations in Wnt/beta-catenin signaling in the kidneys of rats during hypertension, with the severity of these changes depending on the type of hypertension. This study is the first to assess the levels of some elements of the canonical Wnt/beta-catenin signal transduction pathway in various types of arterial hypertension by immunohistochemistry, and may lead to further molecular and functional studies of this pathway in hypertension.
HYPERTENSION RESEARCH
(2021)
Article
Biology
Giacomo L. Glotzer, Pietro Tardivo, Elly M. Tanaka
Summary: The expression of fibroblast growth factors (Fgf) ligands in the Apical Ectodermal Ridge (AER) is a conserved feature of limb development in vertebrates. However, the axolotl, a salamander species, has a unique mesenchymal expression of key Fgf ligands in its developing and regenerating limb. This study investigates the hypothesis that alterations in transcription factors and Wnt signaling during evolution have resulted in this unique expression pattern in the axolotl. The results suggest that a shift in tissue responsiveness to canonical Wnt signaling from epidermis to mesenchyme is one contributing factor to the mesenchymal expression of Fgf ligands in the axolotl.
Article
Microbiology
Chongyang Wang, Ruochen Hu, Liuyuan Duan, Qili Hou, Mengqing Yang, Ting Wang, Haijin Liu, Sa Xiao, Ruyi Dang, Juan Wang, Xinglong Wang, Shuxia Zhang, Zengqi Yang
Summary: This study showed that pseudorabies virus (PRV) infection activates the Wnt/beta-catenin signaling pathway, leading to enhanced virus proliferation and regulation of virus-induced autophagy. Inhibitors of this pathway can reduce PRV titers, while stimulation of the pathway can enhance PRV proliferation. These findings provide potential targets for the development of antiviral agents against PRV.
VETERINARY MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emily P. Y. Yu, Vishal Saxena, Sofia Perin, Marc Ekker
Summary: The dlx genes encode transcription factors that play important roles in craniofacial development. Mutations in dlx5a and dlx5i6 were found to lead to shortened cartilage lengths and altered proliferation of neural crest cells. These mutations also affected the non-canonical Wnt signaling pathway.
Article
Oncology
Astrid Murumagi, Daniela Ungureanu, Suleiman Khan, Mariliina Arjama, Katja Valimaki, Aleksandr Ianevski, Philipp Ianevski, Rebecka Bergstrom, Alice Dini, Anna Kanerva, Riitta Koivisto-Korander, Johanna Tapper, Heini Lassus, Mikko Loukovaara, Andrus Magi, Akira Hirasawa, Daisuke Aoki, Vilja Pietiainen, Teijo Pellinen, Ralf Butzow, Tero Aittokallio, Olli Kallioniemi
Summary: Efforts are being made to develop new therapies for aggressive high-grade serous ovarian cancers (HGSOCs), but the understanding of treatment options for low-grade (LGSOC) or mucinous (MUCOC) ovarian malignancies is lacking. A functional precision oncology (fPO) strategy combining drug testing, genomic profiling and transcriptomic profiling was used to study epithelial ovarian cancers (EOC). Different drug response profiles were observed among HGSOC, LGSOC, and MUCOC PDCs, with LGSOCs responding better to targeted inhibitors. Specific drug responses were identified for each subtype, with potential for individualized therapies in the future.
BRITISH JOURNAL OF CANCER
(2023)
Article
Pharmacology & Pharmacy
Feng Deng, Maren Laasik, Liina Salminen, Lauri Lapatto, Kaisa Huhtinen, Yilin Li, Sampsa Hautaniemi, Johanna Hynninen, Mikko Niemi, Rainer Lehtonen
Summary: The study identified genetic variations in SLCO1B3, LIG3, GSTP1, ABCB1, and OPRM1 associated with risk of adverse effects, treatment response, and prognosis in patients receiving carboplatin-paclitaxel therapy for ovarian cancer.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Review
Oncology
Laszlo Lorenzovici, Laszlo Szilberhorn, Szabolcs Farkas-Raduly, Andrea Ildiko Gasparik, Andreea Mihaela Precup, Adel Gyongyver Nagy, Carsten Utoft Niemann, Tero Aittokallio, Zoltan Kalo, Marcell Csanadi
Summary: This study conducted a systematic literature review to summarize the health economic models related to CLL therapies. The review found that Markov modeling is commonly used to simulate cost effectiveness, but recent studies have added more complexity to the models.
Article
Oncology
Alexandra Lahtinen, Kari Lavikka, Anni Virtanen, Yilin Li, Sanaz Jamalzadeh, Aikaterini Skorda, Anna Rossberg Lauridsen, Kaiyang Zhang, Giovanni Marchi, Veli-Matti Isoviita, Valeria Ariotta, Oskari Lehtonen, Taru A. Muranen, Kaisa Huhtinen, Olli Carpen, Sakari Hietanen, Wojciech Senkowski, Tuula Kallunki, Antti Hakkinen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Summary: Ovarian HGSC is often diagnosed at an advanced stage, with genetically diverse clones existing prior to treatment. This study analyzed whole-genome sequencing data from 510 samples of 148 HGSC patients, revealing three evolutionary states with distinct genomic features, pathways, and phenotypes, which showed significant association with treatment response. Pathway analysis suggested two potential evolutionary trajectories, and experiments with tumor organoids supported targeted therapy for tumors with enriched PI3K/AKT pathway. Heterogeneity analysis indicated more unique clones in samples from the site of origin compared to metastatic tumors or ascites. These findings highlight the importance of integrative tumor evolution analysis for identifying patient subtypes.
Article
Oncology
Sanna Pikkusaari, Manuela Tumiati, Anni Virtanen, Jaana Oikkonen, Yilin Li, Fernando Perez-Villatoro, Taru Muranen, Matilda Salko, Kaisa Huhtinen, Anna Kanerva, Heidi Koskela, Johanna Tapper, Riitta Koivisto-Korander, Titta Joutsiniemi, Ulla-Maija Haltia, Heini Lassus, Sampsa Hautaniemi, Anniina Farkkila, Johanna Hynninen, Sakari Hietanen, Olli Carpen, Liisa Kauppi
Summary: A clinically feasible assay was developed to identify HR-deficient tumors in high-grade serous ovarian cancers. The assay predicted clinical outcomes and helped determine which patients were most likely to benefit from platinum-based chemotherapy and PARP inhibitors.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Swapnil Potdar, Filipp Ianevski, Aleksandr Ianevski, Ziaurrehman Tanoli, Krister Wennerberg, Brinton Seashore-Ludlow, Olli Kallioniemi, Paeivi Ostling, Tero Aittokallio, Jani Saarela
Summary: Functional precision medicine (fPM) simplifies the search for appropriate applications of existing molecules and enhances therapeutic potential. The latest version of Breeze (release 2.0) provides advanced data exploration capabilities and interactive visualization options for accurate interpretation of drug sensitivity and resistance data. It allows integration and cross-comparison of user-uploaded data with publicly available drug response datasets.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemical Research Methods
Anni S. S. Halkola, Kaisa Joki, Tuomas Mirtti, Marko M. M. Maekelae, Tero Aittokallio, Teemu D. D. Laajala
Summary: This paper presents a novel methodology for feature subset selection based on the L-0 pseudonorm, which has advantages in clinical applicability, selection of grouped features, and analysis of high-dimensional transcriptomics data. The methodology is benchmarked against existing regularization methods and shows superior performance.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Oncology
Moritz Otte, Johanna Stachelscheid, Markus Glass, Linus Wahnschaffe, Qu Jiang, Waseem Lone, Aleksandr Ianevski, Tero Aittokallio, Javeed Iqbal, Michael Hallek, Stefan Huettelmaier, Alexandra Schrader, Till Braun, Marco Herling
Summary: T-prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell leukemia. Elevated expression of miR-141/200c cluster in T-PLL cells promotes cell proliferation and alters the expression of genes involved in cell survival and differentiation. Low expression of STAT4, a target gene of miR-141/200c, is associated with an immature phenotype of T-PLL cells and shortened overall survival of T-PLL patients. This study reveals the oncogenic role of miR-141/200c-STAT4 signaling pathway in T-PLL, shedding light on the involvement of non-protein-coding genes in the pathogenesis of this devastating disease.
Article
Biochemistry & Molecular Biology
Juha Saarikettu, Saara Lehmusvaara, Marko Pesu, Ilkka Junttila, Juha Partanen, Petra Sipila, Matti Poutanen, Jie Yang, Teemu Haikarainen, Olli Silvennoinen
Summary: Snd1 is an RNA-binding protein that plays important roles in gene expression. Deletion of Snd1 in mice leads to decreased fertility, organ and body size, and reduced number of myeloid cells with decreased expression of granule protein genes. Moreover, the deletion of Snd1 affects a relatively small number of gene expressions in the spleen and liver, and reveals its function in hypoxia adaptation through negatively regulating hypoxia-related miRNAs and hypoxia-induced transcription.
Article
Obstetrics & Gynecology
Adrian Zegrea, Emilia Ojala, Pia Suvitie, Pirita Varpe, Heikki Huhtinen, Johanna Makela-Kaikkonen, Tero Rautio, Paivi Harkki, Sinikka Salmenkyla, Mika Ukkonen, Maija Lavonius, Tarja Pinta
Summary: This study found that sacral neuromodulation (SNM) may be an effective treatment for refractory chronic pelvic pain in women with endometriosis. Patients experienced pain reduction and improved quality of life after SNM implantation.
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA
(2023)
Review
Oncology
Mona Meng Wang, Sarah E. Coupland, Tero Aittokallio, Carlos R. Figueiredo
Summary: Immune checkpoint therapies can enhance the function of anti-tumour T cells and improve outcomes in cancer patients. However, some patients are refractory to this therapy due to "cold" tumours that do not allow T cell generation or the infiltration of existing anti-tumour T cells. This review explores the mechanisms by which cancer cells induce T cell "desertification" and "exclusion" in these refractory tumours, and highlights the importance of developing immunotherapies that restore T cell generation and tumour trafficking.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Oxana V. Denisova, Joni Merisaari, Riikka Huhtaniemi, Xi Qiao, Laxman Yetukuri, Mikael Jumppanen, Amanpreet Kaur, Mirva Paakkonen, Carina von Schantz-Fant, Michael Ohlmeyer, Krister Wennerberg, Otto Kauko, Raphael Koch, Tero Aittokallio, Mikko Taipale, Jukka Westermarck
Summary: Mitochondrial glycolysis and hyperactivity of the AKT pathway are characteristic of brain tumors, but targeting AKT or PDK has shown limited clinical benefits. In this study, a triplet therapy targeting AKT, PDK, and PP2A was effective in inducing apoptosis in brain tumor cells. Reactivating PP2A converted the cytostatic response to cytotoxic apoptosis by shutting down compensatory mitochondrial oxidative phosphorylation. These findings suggest the potential of targeting mitochondrial metabolism to overcome therapy tolerance in brain tumors.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Teemu D. Laajala, Varsha Sreekanth, Alex C. Soupir, Jordan H. Creed, Anni S. Halkola, Federico C. F. Calboli, Kalaimathy Singaravelu, Michael V. Orman, Christelle Colin-Leitzinger, Travis Gerke, Brooke L. Fridley, Svitlana Tyekucheva, James C. Costello
Summary: Genomic and transcriptomic data from prostate cancer study cohorts can provide valuable insights into the molecular features associated with clinical outcomes. However, these data are often fragmented and not standardized. In this study, we present curatedPCaData, a harmonized data resource that includes over 2900 primary tumor, 200 normal tissue, and 500 metastatic prostate cancer samples across 19 datasets. Our findings demonstrate the potential of meta-analysis in generating robust and clinically meaningful insights.
Article
Biochemical Research Methods
Aikaterini Skorda, Anna Rossberg Lauridsen, Kaisa Huhtinen, Alexandra Lahtinen, Wojciech Senkowski, Jaana Oikkonen, Johanna Hynninen, Sampsa Hautaniemi, Tuula Kallunki
Summary: Patient-derived organoids (PDOs) are ideal ex vivo model systems for studying cancer progression and drug resistance mechanisms. This study presents a protocol for measuring drug efficacy in three-dimensional (3D) high-grade serous ovarian cancer PDO cultures through quantification of cytotoxicity and analyzing proliferation using the Ki67 biomarker.
Article
Medicine, Research & Experimental
Mai T. N. Nguyen, Anna Rajavuori, Kaisa Huhtinen, Sakari Hietanen, Johanna Hynninen, Jaana Oikkonen, Sampsa Hautaniemi
Summary: Circulating tumor DNA (ctDNA) analysis is a promising tool for detecting and profiling cancer genomics changes. However, copy-number analysis for treatment effect monitoring has received less attention compared to mutations. Our study shows that copy-number analysis using a sequencing panel can detect consistent profiles even in low-tumor content ctDNA samples. Longitudinal analysis reveals changes in copy-number profiles in high-tumor content plasma samples, suggesting a relationship between copy-number alterations and relapse. These findings highlight the importance of genomic profiling during treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)