A5053812500- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- RNA Research and Splicing
- Nuclear Structure and Function
- Protein Tyrosine Phosphatases
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Hippo pathway signaling and YAP/TAZ
- ATP Synthase and ATPases Research
- Melanoma and MAPK Pathways
- Prostate Cancer Treatment and Research
- E-commerce and Technology Innovations
- Biochemical and Structural Characterization
- Digital Transformation in Industry
- Skin Protection and Aging
- Immune cells in cancer
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
- Innovation and Socioeconomic Development
University of Turku
2012-2023
Åbo Akademi University
2011-2023
Turku Centre for Computer Science
2019-2023
Turku Centre for Biotechnology
2006-2021
c-Jun NH2-terminal kinases (JNKs) are essential during brain development, when they regulate morphogenic changes involving cell movement and migration. In the adult, JNK determines neuronal cytoarchitecture. To help uncover molecular effectors for JNKs in these events, we affinity purified JNK-interacting proteins from brain. This revealed that stathmin family microtubule-destabilizing SCG10, SCLIP, RB3, RB3′ interact tightly with JNK. Furthermore, SCG10 is also phosphorylated by vivo on...
Defective filopodia formation is linked to pathologies such as cancer, wherein actively protruding filopodia, at the invasive front, accompany cancer cell dissemination. Despite wide biological significance, delineating function in complex systems remains challenging and particularly hindered by lack of compatible methods quantify properties. Here, we present FiloQuant, a freely available ImageJ plugin, detect filopodia-like protrusions both fixed- live-cell microscopy data. We demonstrate...
Pharmacological PP2A activation is a druggable approach to overcome MEK inhibitor resistance.
Integrin trafficking from and to the plasma membrane controls many aspects of cell behavior including motility, invasion, cytokinesis. Recruitment integrin cargo endocytic machinery is regulated by small GTPase Rab21, but detailed molecular mechanisms underlying recruitment are yet unknown. Here we identify an important role for p120RasGAP (RASA1) in recycling endocytosed α/β1-integrin heterodimers membrane. Silencing attenuated augmented motility. Mechanistically, interacted with...
Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated underlies neurological birth defects cancer metastasis. MARCKS-like protein 1 (MARCKSL1) widely expressed in nervous tissue, where, like Jun N-terminal kinase (JNK), it required for neural tube formation, though the mechanism unknown. Here we show that MARCKSL1 directly phosphorylated by JNK on C-terminal residues (S120, T148, T183). This phosphorylation enables to bundle...
Abstract The human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other tyrosine kinases known to regulate their oncogenic signalling, prevailing view on HER2 that this predominantly retained cell surface. Here, we find sortilin-related 1 (SORLA; SORL1 ) co-precipitates with in cancer cells regulates subcellular distribution promoting recycling back plasma membrane. SORLA...
ABSTRACT The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by the LMNA gene, contributes towards altered gene expression during HS, but underlying mechanisms are poorly understood. Here, we show that upon A/C was reversibly phosphorylated at serine 22 concert with HSF1 activation human cells, mouse cells and Drosophila melanogaster vivo. Consequently, phosphorylation facilitated nucleoplasmic localization of nuclear sphericity to...
Increased phosphorylation of the KIF5 anterograde motor is associated with impaired axonal transport and neurodegeneration, but paradoxically also normal transport, though details are not fully defined. JNK phosphorylates KIF5C on S176 in domain; a site that we show phosphorylated brain. Microtubule pelleting assays demonstrate phosphomimetic KIF5C(1-560)S176D associates weakly microtubules compared to KIF5C(1-560)WT. Consistent this, 50% shows diffuse movement neurons. However remaining...
Abstract Current evidence indicates that resistance to the tyrosine kinase-type cell surface receptor (HER2)-targeted therapies is frequently associated with HER3 and active signaling via HER2-HER3 dimers, particularly in context of breast cancer. Thus, understanding response regulation dimer essential decipher therapy relapse mechanisms. Here, we investigate a bidirectional relationship between type-1 transmembrane sorting receptor, sortilin-related (SorLA; SORL1 ). We demonstrate...
Dermal white adipose tissue (dWAT) is involved in the maintenance of skin homeostasis. However, studies concerning its molecular regulation are limited. In present paper, we ask whether introduction two transcription factors, Foxn1 and Hif-1α, into post-wounded Foxn1-/- mice regulates dWAT during wound healing (days 3 6). We have chosen lentivirus vectors (LVs) as a tool to deliver Hif-1α skin. documented that combinations both transgenes reduces number, size diameter dermal adipocytes at...
While organ-confined prostate cancer (PCa) is mostly therapeutically manageable, metastatic progression of PCa remains an unmet clinical challenge. Resistance to anoikis, a form cell death initiated by detachment from the surrounding extracellular matrix, one cellular processes critical for towards aggressive disease. Therefore, further understanding anoikis regulation in might provide therapeutic opportunities. Here, we discover that tumours with concomitant inhibition two tumour suppressor...
Physiological role of luteinizing hormone (LH) and its receptor (LHCGR) in adrenal remains unknown. In inhibin-α/Simian Virus 40 T antigen (SV40Tag) (inhα/Tag) mice, gonadectomy-induced (OVX) elevated LH triggers the growth transcription factor GATA4 (GATA4)-positive adrenocortical tumors a hyperplasia-adenoma-adenocarcinoma sequence.We investigated LHCGR tumor induction, by crossbreeding inhα/Tag with Lhcgr knockout (LuRKO) mice. By knocking out Gata4 Cα1 cells (Lhcgr-ko, Gata4-ko) we...
Abstract Filopodia are commonly observed cellular protrusions in vitro and vivo. Defective filopodia formation is linked to several pathologies including cancer, wherein actively protruding filopodia, at the invasive front, filopodia-mediated probing of microenvironment accompanies cancer cell dissemination. Despite wide biological significance, delineating function these finger-like more complex systems remains technically challenging, particularly hindered by lack compatible methods...
A low tissue oxygen level, < 1% O2, is a typical characteristic inside of solid tumors in head and neck cancer (HNSCC) affecting wide array cell populations, such as macrophages. However, the mechanisms how hypoxia influences macrophages are not yet fully elucidated. Our research aimed to study effect soluble mediators produced by hypoxic cells on macrophage polarization. Furthermore, we studied microenvironment expression tumorigenic toll-like receptor 9 (TLR9) consecutive...
ABSTRACT The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by LMNA gene, has been shown to contribute towards altered gene expression during shock, but the underlying mechanisms are poorly understood. Here we show that reversible A/C phosphorylation at Ser22 upon HS an evolutionary conserved stress triggered concert with HSF1 activation human and mouse cells can also be observed D. melanogaster vivo . Consequently, increase...
ABSTRACT While organ-confined PCa is mostly therapeutically manageable, metastatic progression of remains an unmet clinical challenge. Resistance to anoikis, a form cell death initiated by detachment from the surrounding extracellular matrix, one cellular processes critical for towards aggressive disease. Therefore, further understanding anoikis regulation in might provide therapeutic opportunities. Here, we discover that tumors with concomitantly compromised function two tumor suppressor...
Abstract Despite the pivotal role of phosphatases in cancer cell signalling, systemic understanding phosphatase targets is still at infancy. Protein 2A (PP2A) a human tumor suppressor complex. PP2A inhibition requirement for transformation and regulates many critical signalling pathways. Importantly, emerging data indicates that reactivation activity could provide entirely novel approach therapy. Here, we present first analysis phosphoprotein (dephosphorylome) regulated by cells. Based on...
Current evidence indicates that resistance to HER2-targeted therapies is frequently associated with HER3 and active signaling via HER2-HER3 dimers, particularly in the context of breast cancer. Thus, understanding response regulation dimer per se remains essential decipher therapy relapse mechanisms. Here, we demonstrate by growth factor ligands, heregulins, support transcription a type-1 transmembrane sorting receptor, sortilin-related receptor (SorLA; SORL1 ) downstream mitogen-activated...
Vol. 173 No. 2, April 24, 2006. Pages [265–277][1]. The following errors occur in this paper. All instances of “JIP” alone should read “JNK-interacting protein”, whereas “JIP1” refers specifically to the JIP family protein also known as MAPK8IP1. The legend for Fig. 9 B
Abstract The mechanisms promoting re-growth of dormant cancer cells under continuous tyrosine kinase inhibitor (TKI) therapy are poorly understood. Here we present transcriptional profiling HER2+ breast treated continuously with HER2 TKI (HER2i) for 9 months. data reveals specific gene regulatory programs associated transition from drug tolerant persister (DTPs) to proliferating DTEP (drug expanding persister) and eventually long-term resistance. Focusing on yet understood phosphatases as...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)
Abstract Human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. Endosomal trafficking of many other tyrosine kinases regulates their oncogenic signaling, but the prevailing view that HER2 retained on cell surface. Here we reveal in cancer cells Sortilin related 1 (SORLA; SORL1 ) forms a complex with its subcellular distribution promoting recycling endosomal back to plasma membrane. Expression SORLA lines bladder...