Review
Developmental Biology
Naoya Yamaguchi, Holger Knaut
Summary: Cell-extracellular matrix interactions are essential for cell anchoring and migration, with focal adhesions (FAs) playing a key role. However, the role of FAs in vivo is still not well understood.
Article
Microbiology
Courtney M. Klappenbach, Nicholas M. Negretti, Jesse Aaron, Teng-Leong Chew, Michael E. Konkel
Summary: Our study reveals that C. jejuni infection alters the size and topology of focal adhesions in epithelial cells, leading to changes in cell adhesion strength and motility. The increased phosphorylation of paxillin and altered turnover at focal adhesions may contribute to the effects on cell behavior. Additionally, inhibiting protein synthesis or using specific mutants of C. jejuni can partially reverse these effects, suggesting a potential mechanism for the observed restricted intestinal repair in infected animals.
Article
Biochemistry & Molecular Biology
Yu-Shan Lin, Yi-Hsin Lin, MyHang Nguyen Thi, Shih-Chuan Hsiao, Wen-Tai Chiu
Summary: The dysregulation of store-operated Ca2+ entry (SOCE) is associated with cancer progression. Upregulation of stromal interaction molecule 1 (STIM1) promotes cancer cell migration, invasion, and metastasis, while excessive Ca2+ can have a negative impact on cancer metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Narendra Thapa, Tianmu Wen, Vincent L. Cryns, Richard A. Anderson
Summary: This article focuses on the processes of cell adhesion and migration in cancer cells, specifically discussing the reorganization of microtubule cytoskeleton, cell polarity, and phosphoinositide signaling and their impact on adhesion and migration.
Article
Cell Biology
Xinyi Ren, Xiaopu Guo, Zihan Liang, Renxian Guo, Shaohui Liang, Han Liu
Summary: Cell migration is a complex process that involves the coordination of various cellular components. In this study, we discovered a novel interaction between IQGAP1 and Hax1, which plays a significant role in focal adhesion turnover and directional cell migration. Our findings suggest that Hax1 acts as a link between dynamic focal adhesions and IQGAP1, facilitating efficient cell migration. Perturbation of the IQGAP1/Hax1 interaction impairs focal adhesion turnover and inhibits directional cell migration.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Elizabeth Riffo, Mario Palma, Matias Hepp, Diego Benitez-Riquelme, Vicente A. Torres, Ariel F. Castro, Roxana Pincheira
Summary: SALL2/Sall2 is a transcription factor associated with development, neuronal differentiation, and cancer. Sall2 promotes cell migration by modulating focal adhesion dynamics and transcriptionally regulating integrin beta 1 expression and FAK autophosphorylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Elizabeth Riffo, Mario Palma, Matias Hepp, Diego Benitez-Riquelme, Vicente A. Torres, Ariel F. Castro, Roxana Pincheira
Summary: SALL2/Sall2 is a transcription factor that plays a positive role in cell migration, and its deficiency can lead to decreased cell motility and altered focal adhesion dynamics. Sall2 promotes cell migration by regulating integrin beta 1 expression and FAK autophosphorylation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Developmental Biology
Hannah M. Olson, Alex V. Nechiporuk
Summary: Collective cell migration involves coordinated migratory behavior of cell cohorts. Protrusive behavior in the zebrafish posterior lateral line primordium (pLLP) is regulated by the Arp2/3 complex, leading to the formation of brush-like protrusions that aid in migration towards the overlying skin. Disruption of focal adhesion complexes surrounding the pLLP impairs migration, with Erk signaling playing a key role in the proper formation of protrusions and pLLP migration.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Carsten Baltes, Divyendu Goud Thalla, Uli Kazmaier, Franziska Lautenschlaeger
Summary: Actin plays a crucial role in maintaining cell shape and generating forces. By stabilizing actin filaments with miuraenamide A, we observed a decrease in filament dynamics and an elongation of filament length, resulting in altered cell migration speed and nuclear position.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Jie Liu, Zhongzhen Liu, Keng Chen, Wei Chen, Xiyuan Fang, Meng Li, Xuening Zhou, Ning Ding, Huan Lei, Chen Guo, Tao Qian, Yilin Wang, Lin Liu, Yonglong Chen, Hui Zhao, Ying Sun, Yi Deng, Chuanyue Wu
Summary: Cell migration involves front-to-rear asymmetric focal adhesion (FA) dynamics, which facilitates trailing edge detachment and directional persistence. Here, we show that kindlin-2 is crucial for FA sliding and disassembly in migrating cells. Loss of kindlin-2 markedly reduced FA number and selectively impaired rear FA sliding and disassembly, resulting in defective rear retraction and reduced directional persistence during cell migration.
JOURNAL OF CELL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Jianjiang Hu, Xiaowei Gong, Staffan Stromblad
Summary: Cells probe their microenvironment using membrane protrusion-retraction cycles. Spatial and temporal coordination between Rac1 and RhoA GTP-binding activities play critical roles in initiating and reinforcing protrusions and retractions. Rac1-GTP levels increase before protrusions, while RhoA-GTP levels increase before retractions. Rac1-GTP nadirs and peaks coincide with maximal edge velocity of local membrane protrusions and retractions, followed by declined edge velocity. The alteration of local Rac1-GTP precedes the alteration of traction force. Through optogenetic Rac1-GTP perturbations, we demonstrate the fundamental role of Rac1 in restricting the size and durability of protrusions and retractions, possibly through controlling traction forces.
Review
Cell Biology
Julio C. C. Fierro Morales, Qian Xue, Minna Roh-Johnson
Summary: Cell-substrate adhesion is crucial for cell migration, with focal adhesions being a well-studied structure involved in this process. However, the understanding of the evolution and in vivo role of cell-substrate adhesion machinery is limited. Further investigation in these areas is important for understanding the role of cell-substrate adhesion in physiological contexts and for potential applications in adhesion-based processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biology
Karin Legerstee, Adriaan B. Houtsmuller
Summary: The cytoskeleton provides structure and support to cells, with focal adhesions linking actin fibres to the extracellular matrix and contributing to cell migration. Recent research on focal adhesions has revealed a layered structure composed of different proteins, each layer playing a specific role in cell adhesion and migration. This new understanding sheds light on the mechanisms underlying cell movement and interaction with the extracellular environment.
Article
Multidisciplinary Sciences
Yuh-Ru Julie Lee, Soichiro Yamada, Su Hao Lo
Summary: Biomolecular condensates formed by liquid-liquid phase separation include GFP-tagged tensin-1 (TNS1) proteins. Live-cell imaging revealed that TNS1 condensates emerge from the disassembling ends of focal adhesions (FAs) and their presence is cell cycle dependent. TNS1 condensates dissolve prior to mitosis and reappear when postmitotic daughter cells form new FAs, containing selected FA proteins and signaling molecules.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Ha Hyung Moon, Nina-Naomi Kreis, Alexandra Friemel, Susanne Roth, Dorothea Schulte, Christine Solbach, Frank Louwen, Juping Yuan, Andreas Ritter
Summary: The microtubule cytoskeleton regulator MCAK plays a critical role in cell motility and migration by affecting the dynamics of actin-MT cytoskeleton and FA turnover, potentially promoting malignant progression and metastasis of tumor cells.
Article
Multidisciplinary Sciences
Ievgenia Pastushenko, Federico Mauri, Yura Song, Florian de Cock, Bob Meeusen, Benjamin Swedlund, Francis Impens, Delphi Van Haver, Matthieu Opitz, Manuel Thery, Yacine Bareche, Gaelle Lapouge, Marjorie Vermeersch, Yves-Remi Van Eycke, Cedric Balsat, Christine Decaestecker, Youri Sokolow, Sergio Hassid, Alicia Perez-Bustillo, Beatriz Agreda-Moreno, Luis Rios-Buceta, Pedro Jaen, Pedro Redondo, Ramon Sieira-Gil, Jose F. Millan-Cayetano, Onofre Sanmatrtin, Nicky D'Haene, Virginie Moers, Milena Rozzi, Jeremy Blondeau, Sophie Lemaire, Samuel Scozzaro, Veerle Janssens, Magdalena De Troya, Christine Dubois, David Perez-Morga, Isabelle Salmon, Christos Sotiriou, Francoise Helmbacher, Cedric Blanpain
Summary: This study reveals that mutation of the FAT1 gene promotes tumor initiation, progression, invasiveness, stemness, and metastasis. Loss of function of FAT1 activates a CAMK2-CD44-SRC axis while inactivates EZH2, playing important roles in the expression of YAP1 and ZEB1.
Review
Biochemistry & Molecular Biology
Iris Verbinnen, Pieter Vaneynde, Sara Reynhout, Lisa Lenaerts, Rita Derua, Gunnar Houge, Veerle Janssens
Summary: In this review, the authors examine the impact of PP2A gene mutations on neurodevelopmental disorders and intellectual disability, with a focus on PPP2CA, PPP2R1A, and PPP2R5D. They provide insights into how these mutations affect PP2A structure, substrate specificity, and potential function in neurobiology and brain development.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Oncology
Bob Meeusen, Emanuela Elsa Cortesi, Judit Domenech Omella, Anna Sablina, Juan-Jose Ventura, Veerle Janssens
Summary: This study found that the loss of PP2A activator PTPA in KRAS-mutant lung adenocarcinomas is associated with poorer overall survival, increased cell growth, and accelerated tumor formation. Additionally, the depletion of PPP2R4 induced resistance against MEK inhibitor but sensitized cells to mTOR inhibitor, highlighting its clinical relevance in NSCLC etiology and kinase inhibitor response.
Article
Cell Biology
Emanuela E. Cortesi, Bob Meeusen, Arno Vanstapel, Stijn E. Verleden, Bart M. Vanaudenaerde, Wim A. Wuyts, Wim Janssens, Veerle Janssens, Tania Roskams, Juan-Jose Ventura
Summary: Research indicates an elevated expression of LGR6 in abnormal lung epithelial progenitors in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with an increase in senescence-associated markers in these cells. Through chronic activation of the Wnt/beta-catenin pathway, LGR6 mediates the impairment and exhaustion of epithelial progenitors in both diseases.
Article
Genetics & Heredity
Nora Oyama, Pieter Vaneynde, Sara Reynhout, Emily M. Pao, Andrew Timms, Xiao Fan, Kimberly Foss, Rita Derua, Veerle Janssens, Wendy Chung, Ghayda M. Mirzaa
Summary: This study delineates the common features of PPP2R5D-related neurodevelopmental disorders, expands the clinical and molecular spectrum, and identifies genotype-phenotype correlations.
JOURNAL OF MEDICAL GENETICS
(2023)
Review
Cell Biology
Pieter Vaneynde, Iris Verbinnen, Veerle Janssens
Summary: Reversible protein phosphorylation is a fundamental regulatory mechanism in eukaryotic cell and organismal physiology. Mutations in serine/threonine protein phosphatases (PSP) have been found to be associated with congenital diseases, most of which are characterized by brain-specific abnormalities. Understanding the pathogenic mechanisms of these diseases and identifying downstream targets and effectors could potentially lead to new therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Iris Verbinnen, Sara S. S. Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A. A. King
Summary: PP2A-related (neuro) developmental disorders are genetic diseases caused by genetic alterations in the genes encoding subunits of type 2A protein phosphatases. This study reports a case of PPP2CA-affected individual with a novel de novo missense variant, and evaluates its pathogenicity. Clinically, the patient presented with developmental delay, dysmorphic facial features, seizures, and autistic behaviors. This study reveals a milder manifestation of clinical and molecular spectrum in PPP2CA cases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Raquel L. Arribas, Lucia Viejo, Isaac Bravo, Minerva Martinez, Eva Ramos, Alejandro Romero, Eva M. Garcia-Frutos, Veerle Janssens, Carmen Montiel, Cristobal de los Rios
Summary: Protein phosphatase 2A (PP2A) plays a crucial role in cellular processes and its deficiency is associated with severe pathologies. In Alzheimer's disease, the hyperphosphorylation of tau protein is linked to the depression of PP2A activity. Researchers have designed new ligands to prevent PP2A inhibition, with compound 10 showing the most promising outcomes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Jos van Pelt, Bob Meeusen, Rita Derua, Liesbeth Guffens, Eric Van Cutsem, Veerle Janssens, Chris Verslype
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a low survival and little therapeutic advancements are expected. Epithelial-to-Mesenchymal transition (EMT) and Protein Phosphatase Type 2A (PP2A) play a role in aggressive PDAC. This study investigates the relationship between PP2A expression signature and EMT, and explores treatment implications.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Karolina Pavic, Nikhil Gupta, Judit Domenech Omella, Rita Derua, Anna Aakula, Riikka Huhtaniemi, Juha A. Maatta, Nico Hofflin, Juha Okkeri, Zhizhi Wang, Otto Kauko, Roosa Varjus, Henrik Honkanen, Daniel Abankwa, Maja Kohn, Vesa P. Hytonen, Wenqing Xu, Jakob Nilsson, Rebecca Page, Veerle Janssens, Alexander Leitner, Jukka Westermarck
Summary: This study reveals the molecular level details and structural mechanisms of PP2A-B56 alpha inhibition by the oncoprotein CIP2A. CIP2A displaces the PP2A-A subunit and forms a pseudotrimer, blocking the B56 alpha substrate binding site and stabilizing CIP2A protein.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Judit Domenech Omella, Emanuela E. Cortesi, Iris Verbinnen, Michiel Remmerie, Hanghang Wu, Francisco J. Cubero, Tania Roskams, Veerle Janssens
Summary: The deletion of Ppp2r5d gene accelerates the development of hepatocellular carcinoma (HCC) in a mouse model of DEN-induced hepatocarcinogenesis, suggesting its tumor-suppressive function. The deletion of Ppp2r5d also leads to the development of HCC and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and may regulate its own expression to restrict tumor growth.
Editorial Material
Cell Biology
Veerle Janssens, Brian E. Wadzinski, Chenchen Li, Richard E. Honkanen
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Judit Domenech Omella, Bob Meeusen, Emanuela Cortesi, Karen Zwaenepoel, Rita Derua, Chris Verslype, Patrick Pauwels, Jukka Westermarck, Tania Roskams, Jos van Pelt, Veerle Janssens
JOURNAL OF HEPATOLOGY
(2022)
Article
Nutrition & Dietetics
Veronika Kloubert, Inga Wessels, Jana Wolf, Karoline Blaabjerg, Veerle Janssens, Jan Hapala, Wolfgang Wagner, Lothar Rink
Summary: The study revealed that zinc deficiency leads to reduced IL-2 expression in T cells due to enhanced PP2A and HDAC1 activity, and a molecular link through the transcription factor CREMa was uncovered in connecting zinc deficiency with this decreased IL-2 production.
CLINICAL NUTRITION
(2021)
Article
Genetics & Heredity
Lisa Lenaerts, Sara Reynhout, Iris Verbinnen, Frederic Laumonnier, Annick Toutain, Frederique Bonnet-Brilhault, Yana Hoorne, Shelagh Joss, Anna K. Chassevent, Constance Smith-Hicks, Bart Loeys, Pascal Joset, Katharina Steindl, Anita Rauch, Sarju G. Mehta, Wendy K. Chung, Koenraad Devriendt, Susan E. Holder, Tamison Jewett, Lauren M. Baldwin, William G. Wilson, Shelley Towner, Siddharth Srivastava, Hannah F. Johnson, Cornelia Daumer-Haas, Martina Baethmann, Anna Ruiz, Elisabeth Gabau, Vani Jain, Vinod Varghese, Ali Al-Beshri, Stephen Fulton, Oded Wechsberg, Naama Orenstein, Katrina Prescott, Anne-Marie Childs, Laurence Faivre, Sebastien Moutton, Jennifer A. Sullivan, Vandana Shashi, Suzanne M. Koudijs, Malou Heijligers, Emma Kivuva, Amy McTague, Alison Male, Yvette van Ierland, Barbara Plecko, Isabelle Maystadt, Rizwan Hamid, Vickie L. Hannig, Gunnar Houge, Veerle Janssens
Summary: We significantly expand the phenotypic spectrum of PPP2R1A-related NDD, revealing a broader clinical presentation of the patients and that the functional consequences of the variants are more diverse than previously reported.
GENETICS IN MEDICINE
(2021)