Article
Cell Biology
James Osei-Owusu, Junhua Yang, Ka Ho Leung, Zheng Ruan, Wei Lu, Yamuna Krishnan, Zhaozhu Qiu
Summary: The proton-activated Cl- (PAC) channel has been identified as a low pH sensor in endosomes, preventing hyper-acidification by releasing Cl- from the lumen.
Article
Cell Biology
Sandra Tavares, Nalan Liv, Milena Pasolli, Mark Opdam, Max A. K. Ratze, Manuel Saornil, Lilian M. Sluimer, Rutger C. C. Hengeveld, Robert van Es, Erik van Werkhoven, Harmjan Vos, Holger Rehmann, Boudewijn M. T. Burgering, Hendrika M. Oosterkamp, Susanne M. A. Lens, Judith Klumperman, Sabine C. Linn, Patrick W. B. Derksen
Summary: Elevated expression of non-receptor tyrosine kinase FER is associated with poor prognosis in breast cancer patients, particularly in high-grade and basal/triple-negative cases. However, high FER levels are correlated with improved outcomes after adjuvant taxane-based chemotherapy in high-risk, HER2-negative patients. Mechanistic studies reveal that FER regulates endosomal recycling and its inhibition leads to reduced breast cancer cell invasion. Furthermore, DCTN2 is identified as a substrate of FER, and its phosphorylation at tyrosine 6 is essential for tubular recycling domains formation and TNBC cell invasion.
Article
Multidisciplinary Sciences
Alison Boutet, Carlos Zeledon, Gregory Emery
Summary: Chemotaxis is important for diverse migrations in development and diseases like cancer progression. In this study, the researchers investigated the role of ArfGAP1 in regulating chemotaxis during collective cell migration. They found that ArfGAP1 is required to maintain receptor tyrosine kinases at the plasma membrane, and its absence leads to decreased active receptors and increased late endosomes. They also observed increased late endosomes and lysosomes in the absence of ArfGAP1, and identified genetic interactions with Lrrk in receptor sorting.
Article
Biochemistry & Molecular Biology
Zuodong Ye, Dawei Wang, Yingying Lu, Yunjiao He, Jingting Yu, Wenjie Wei, Chang Chen, Rui Wang, Liang Zhang, Liangren Zhang, Minh T. N. Le, William C. Cho, Mengsu Yang, Hongmin Zhang, Jianbo Yue
Summary: V1 shows significant anti-metastatic activity by inhibiting cancer cell migration and metastasis in vitro and in vivo, as well as suppressing colony formation, migration, and invasion of cancer cells. V1 targets CapZ beta to inhibit endosomal trafficking and metastasis processes.
Article
Biology
Dawei Wang, Zuodong Ye, Wenjie Wei, Jingting Yu, Lihong Huang, Hongmin Zhang, Jianbo Yue
Summary: The study reveals that CapZ regulates endosomal trafficking by controlling the density of F-actin around early endosomes and recruiting RAB5 effectors.
Article
Multidisciplinary Sciences
Maisel J. Caliva, Won Seok Yang, Shirley Young-Robbins, Ming Zhou, Hana Yoon, Michelle L. Matter, Mark L. Grimes, Thomas Conrads, Joe William Ramos
Summary: Endosomal trafficking of integrins modulates cell motility, with PEA-15 enriching in endosomes, promoting endosomal internalization of α5β1 integrin and cellular migration, where the promotion of migration by PEA-15 is dependent on phosphorylation at specific serine sites.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Icten Meras, Laetitia Chotard, Thomas Liontis, Zakaria Ratemi, Benjamin Wiles, Jung Hwa Seo, Jeremy M. Van Raamsdonk, Christian E. Rocheleau
Summary: This study reveals that endosomal localization is a mechanism regulating the FOXO transcription factor DAF-16, which plays important roles in metabolism and aging. The endosomal localization of DAF-16 is modulated by endosomal trafficking proteins, and manipulating DAF-16's localization affects its functions in lifespan regulation and gene expression.
Article
Biochemistry & Molecular Biology
Taslima Gani Khan, David Ginsburg, Brian T. Emmer
Summary: RAB10 regulates the uptake of LDL and transferrin in hepatocytes by promoting the recycling of their respective receptors from specific compartments.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Chemistry, Analytical
Hyunbin Kim, Hae Nim Lee, Jaesik Choi, Jihye Seong
Summary: Internalized B2ARs can sustain their activity and cAMP production for several hours during the endosomal trafficking pathway. The temporal kinetics of B2AR activity can be well explained by an active-vesicle population model modified from the Ricker model.
ANALYTICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Anne Mette G. Jensen, Yu Kitago, Elnaz Fazeli, Christian B. Vaegter, Scott A. Small, Gregory A. Petsko, Olav M. Andersen
Summary: SORL1 gene, encoding SORLA protein, is the fourth gene associated with Alzheimer's disease (AD) and linked to both early- and late-onset forms of the disease. SORLA interacts with retromer, regulating the recycling of endosomal cargo. This study provides a structural model for how SORLA folds and fits into retromer-positive endosomal tubules, showing its dimerization and enhancing retromer-dependent recycling of APP.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Xueyu Wang, Zhiqiang Wei, Tingyu Lan, Yulin He, Bin Cheng, Ruimin Li, Hongxia Chen, Fahong Li, Guohua Liu, Bin Jiang, Yong Lin, Mengji Lu, Zhongji Meng
Summary: CCDC88A/GIV enhances HBV replication by increasing endosomal trafficking and reducing autophagic degradation of HBV antigens. This suggests that CCDC88A/GIV-mediated endosomal trafficking plays a significant role in HBV replication and progeny secretion.
Article
Biochemistry & Molecular Biology
Hussein Al-Akhrass, James R. W. Conway, Annemarie Svane Aavild Poulsen, Ilkka Paatero, Jasmin Kaivola, Artur Padzik, Olav M. Andersen, Johanna Ivaska
Summary: Resistance to HER2-targeted therapies in breast cancer is often associated with HER3 signaling, and the interaction between SorLA and HER3 has been found to play a key role in regulating the stability of the HER2-HER3 dimer. Loss of SorLA compromises heregulin-induced cell proliferation and sensitizes metastatic anti-HER2 therapy-resistant cells to neratinib, indicating a potential therapeutic target for overcoming resistance mechanisms.
Article
Biochemistry & Molecular Biology
Vanesa Madan, Lucas Albacete-Albacete, Li Jin, Pietro Scaturro, Joseph L. Watson, Nadine Muschalik, Farida Begum, Jerome Boulanger, Karl Bauer, Michael A. Kiebler, Emmanuel Derivery, Simon L. Bullock
Summary: HEATR5B is a novel player in dynein-dynactin function, directly binding to the dynein tail and dynactin, and stimulating the motility of AP1-associated endosomal membranes. HEATR5B also promotes association of AP1 with endosomal membranes independently of dynein.
Article
Neurosciences
Anne Rovelet-Lecrux, Sebastien Feuillette, Laetitia Miguel, Catherine Schramm, Segolene Pernet, Olivier Quenez, Isabelle Segalas-Milazzo, Laure Guilhaudis, Stephane Rousseau, Gaetan Riou, Thierry Frebourg, Dominique Campion, Gael Nicolas, Magalie Lecourtois
Summary: The SorLA protein, encoded by the SORL1 gene, plays a crucial role in the pathophysiology of Alzheimer's disease (AD) by regulating A beta peptide production. Identified missense variants of SORL1 in AD patients can lead to altered maturation and trafficking of the SorLA protein, impacting its function and potentially increasing the risk of AD. This study demonstrates a novel pathophysiological mechanism linking specific SorLA missense variants to impaired cellular trafficking, ultimately affecting A beta secretion and associating with AD pathophysiology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Winona Onglao, Yeesim Khew-Goodall, Leila Belle, Ana Lonic
Summary: Targeting a single TK/RTK in solid cancer treatment has not been as successful as in blood cancers, partly due to acquired resistance and upregulation of compensatory RTK signaling. Instead of inhibiting individual compensatory RTKs, universally inhibiting signaling from multiple RTKs may prove to be a more effective approach.
Article
Oncology
Liisa Porra, Lauri Wendland, Tiina Seppala, Hanna Koivunoro, Hannu Revitzer, Jussi Tervonen, Leena Kankaanranta, Anu Anttonen, Mikko Tenhunen, Heikki Joensuu
Summary: The authors reviewed the results of 249 patients treated with boron neutron capture therapy (BNCT) at Helsinki University Hospital, Finland. They found that BNCT using l-boronophenylalanine-fructose (l-BPA-F) as the boron delivery agent was well tolerated and showed efficacy in the treatment of head and neck cancer and malignant glioma. They also described a new hospital BNCT facility that integrates a proton accelerator-based neutron source for treatment planning and positioning.
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
(2023)
Article
Oncology
Ke Peng, Feifei Zhang, Yichen Wang, Pranshu Sahgal, Tianxia Li, Jin Zhou, Xiaoyan Liang, Yanxi Zhang, Nilay Sethi, Tianshu Liu, Haisheng Zhang, Adam J. Bass
Summary: The study aims to identify the resistance mechanisms to FAK inhibitors in diffuse gastric cancer (DGC) and evaluate the efficacy of combining FAK inhibitors with CDK4/6 inhibitors or MAPK inhibitors. The results showed that CDK6 promoted resistance to FAK inhibitors and FAK inhibitor treatment activated the MAPK pathway. Furthermore, the combination of CDK4/6 inhibitors or MAPK inhibitors enhanced the efficacy of FAK inhibitors.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Anna Aakula, Aleksi Isomursu, Christian Rupp, Andrew Erickson, Nikhil Gupta, Otto Kauko, Pragya Shah, Artur Padzik, Yuba Raj Pokharel, Amanpreet Kaur, Song-Ping Li, Lloyd Trotman, Pekka Taimen, Antti Rannikko, Jan Lammerding, Ilkka Paatero, Tuomas Mirtti, Johanna Ivaska, Jukka Westermarck
Summary: This study found that prostate cancer tumors with concomitant inhibition of PP2A and PTEN are particularly aggressive, with low patient survival rates. Overexpression of PME-1 inhibits anoikis in PTEN-deficient prostate cancer cells. The results suggest that PME-1 may be a candidate biomarker for particularly aggressive PTEN-deficient prostate cancer.
MOLECULAR ONCOLOGY
(2023)
Article
Engineering, Biomedical
Cameron Wright, Pietari Makela, Alexandre Bigot, Mikael Anttinen, Peter J. Bostrom, Roberto Blanco Sequeiros
Summary: This study aimed to develop a deep learning model capable of predicting the non-perfused volume (NPV) immediately after prostate ablation therapy without the need for MRI contrast agents. The model was trained and tested using MRI imaging data from 95 patients, and the results showed the feasibility of predicting NPV without the use of MRI contrast agents, which could improve patient treatment outcomes.
BIOMEDICAL ENGINEERING LETTERS
(2023)
Article
Oncology
Heikki Joensuu, Eva Wardelmann, Mikael Eriksson, Annette Reichardt, Kirsten Sundby Hall, Jochen Schuette, Silke Cameron, Peter Hohenberger, Harri Sihto, Philipp J. Jost, Lars H. Lindner, Sebastian Bauer, Bengt Nilsson, Raija Kallio, Tommi Pesonen, Peter Reichardt
Summary: This study found that patients with KIT exon 11 deletion/indel mutation in gastrointestinal stromal tumor (GIST) had longer overall survival (OS) and recurrence-free survival (RFS) when treated with 3 years of adjuvant imatinib compared to 1 year of treatment. However, patients with KIT exon 9 mutation had poor OS regardless of the duration of adjuvant imatinib treatment.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Katri Vaparanta, Anne Jokilammi, Ilkka Paatero, Johannes A. Merilahti, Juho Heliste, Karthik Amudhala Hemanthakumar, Riikka Kivela, Kari Alitalo, Pekka Taimen, Klaus Elenius
Summary: In this study, it is demonstrated that Neuregulin-1 (NRG-1) regulates myocardial growth through the STAT5b pathway. Disruption of the NRG-1/ERBB4 pathway or inhibition of Dynamin-2 reduces STAT5b activation and cardiomyocyte hypertrophy. Activation of Stat5 is also observed in NRG-1-induced myocardial growth in zebrafish embryos, and knockdown of stat5b leads to reduced myocardial growth and cardiac function. Furthermore, the NRG-1/ERBB4/STAT5b pathway is differentially regulated in patients with pathological cardiac hypertrophy.
Article
Biochemistry & Molecular Biology
Kaisa Lehtomaki, Eetu Heerva, Pirkko-Liisa Kellokumpu-Lehtinen, Harri Mustonen, Tapio Salminen, Heikki Joensuu, Kethe Hermunen, Mogens Karsbol Boisen, Julia Sidenius Johansen, Caj Haglund, Pia Osterlund
Summary: Based on the analysis of clinical data from patients with colorectal cancer undergoing adjuvant chemotherapy, it was found that CEA levels transiently increased in about half of the patients during the treatment. Compared to patients with a persistent increase, those with transiently increased CEA had better outcomes in terms of disease-free survival and overall survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Johanna Orling, Katri Kosonen, Jenna Villman, Martin Reichard, Ilkka Paatero
Summary: Impaired wound healing associated with aging has significant impacts on human health and healthcare sector. Deficient angiogenesis may contribute to this process, but the underlying biology is still poorly understood due to complexities and costs in using mammalian aging models. In this study, zebrafish and turquoise killifish fin regeneration models were used to investigate aging-related vascular biology of impaired wound healing. The results showed reduced regeneration in the old individuals of both species, accompanied by changes in angiogenesis, vascular density, and expression levels of angiogenesis biomarker VEGF-A. Anti-angiogenic drug SU5416 further reduced regeneration, suggesting the crucial role of angiogenesis in the regeneration of aging caudal fin despite age-related changes in vasculature. These fish fin regeneration models are therefore suitable for studying aging-related decline in wound healing and associated alterations in aging vasculature.
Article
Dermatology
Anna-stiina Merilaeinen, Maria Von Willebrand-Backman, Harri Sihto, Virve Koljonen
Summary: This study retrospectively examined the records of patients with eccrine porocarcinoma and found that there was no significant difference between wide local excision only and wide local excision with sentinel lymph node biopsy groups. Further studies and international collaboration are needed.
ACTA DERMATO-VENEREOLOGICA
(2023)
Article
Gastroenterology & Hepatology
Anil K. Giri, Mervi Aavikko, Linnea Wartiovaara, Toni Lemmetyinen, Juha Karjalainen, Juha Mehtonen, Kimmo Palin, Niko Valimaki, Max Tamlander, Riikka Saikkonen, Auli Karhu, Ekaterina Morgunova, Benjamin Sun, Heiko Runz, Priit Palta, Shuang Luo, Heikki Joensuu, Tomi P. Makela, Iiro Kostiainen, Camilla Schalin-Jantti, Aarno FinnGen, Aarno Palotie, Lauri A. Aaltonen, Saara Ollila, Mark J. Daly
Summary: This study is the largest genome-wide association study on small intestinal neuroendocrine tumors (SI-NETs) to date, and it identified 6 significant loci associated with SI-NET risk. Four of these loci are novel, and one of the top hits is a missense variant in the LGR5 gene, a marker of adult intestinal stem cells.
Article
Developmental Biology
Ilkka Paatero
Summary: Power outages can occur at any time and place for various reasons, posing a threat to scientific research in biology. Aquatic animal husbandry, in particular, is vulnerable as the animals' well-being relies on uninterrupted electricity supply, and years of scientific work may be impacted by the condition of these animal stocks. Therefore, it is crucial to have tools for estimating and managing these risks. This study utilizes modeling to assess temperature changes in aquarium water during power outages and develops simplified models for zebrafish facilities. Additionally, a calculation worksheet is provided to assist in modeling the kinetics of water temperature changes.
Article
Oncology
Verneri Virtanen, Kreetta Paunu, Antti Kukkula, Saana Niva, Ylva Junila, Mervi Toriseva, Terhi Jokilehto, Sari Makela, Riikka Huhtaniemi, Matti Poutanen, Ilkka Paatero, Maria Sundvall
Summary: The downregulation of l-CaD, regulated by GR, reduces the metastatic potential of PCa, both in vitro and in vivo. CALD1 gene is co-expressed with GR and GR activation upregulates l-CaD expression. This indicates that l-CaD is involved in PCa metastasis and its expression is clinically relevant in the development of antiandrogen resistance.
Review
Oncology
Heikki Joensuu
Summary: Gastrointestinal stromal tumor (GIST) is a common sarcoma arising from the gastrointestinal tract, mainly the stomach, with varying malignancy potential. Surgery is generally curative for localized GISTs. Adjuvant imatinib has been shown to improve recurrence-free survival and overall survival (OS) in high-risk GIST patients with an imatinib-sensitive mutation.
Article
Multidisciplinary Sciences
Pranshu Sahgal, Deepa T. Patil, Pratyusha Bala, Zsofia M. Sztupinszki, Viktoria Tisza, Sandor Spisak, Anna G. Luong, Brandon Huffman, Aurel Prosz, Harshabad Singh, Jean-Bernard Lazaro, Zoltan Szallasi, James M. Cleary, Nilay S. Sethi
Summary: This study found that there is activation of replication stress, DNA damage response (DDR), and p21 in the progression of gastric cancer. Specific DDR biomarkers and ploidy abnormalities can predict the progression of premalignant lesions and the response to DDR pathway inhibitors.
Article
Oncology
Kirsi Toivanen, Sami Kilpinen, Kalle Ojala, Nanna Merikoski, Sami Salmikangas, Mika Sampo, Tom Bohling, Harri Sihto
Summary: By analyzing the RNA sequences and signaling pathways of liposarcoma samples, we identified subtype-specific genes and their expression patterns. PDE3A modulators were found to have potential as drugs for treating myxoid liposarcoma. Further studies are needed to develop these drugs for clinical use.