Browsing by Subject "Cell polarity"

Now showing 1 - 3 of 3
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    Crumbs3: Expression and biological significance in normal and neoplastic tissues
    (2026) Akane Kitta-Kunihiro; Chiemi Ikude; Eisaku Kondo; Hidekazu Iioka; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Cellular polarity plays a fundamental role in tissue organization and homeostasis, and its disruption is closely linked to tumorigenesis. Crumbs3 (CRB3), a conserved polarity protein, is essential for epithelial morphogenesis, tight-junction formation, and barrier function. This review summarizes current knowledge regarding CRB3 expression in normal and malignant human tissues and its dual roles in cancer progression. Systematic immunohistochemical analyses revealed strong CRB3 expression in non-neoplastic glandular epithelia of the gastrointestinal, hepato-pancreato-biliary, renal, and respiratory tracts, as well as in fetal tissues, suggesting its importance in organ development and maintenance. In neoplastic tissues, represented by colorectal adenocarcinoma and oral squamous cell carcinoma, CRB3 expression is preserved or even enhanced compared with normal tissues, which promotes tumor cell migration, triggering invasion/ metastasis as well as cellular proliferation through signaling pathways involving FGFR and RhoA activation. Conversely, previous studies reported that CRB3 functions as a tumor suppressor, based on findings that CRB3 expression induces loss of epithelial mesenchymal transition, whereas loss of CRB3 expression attenuates the integrity of tight junctions, resulting in significantly poorer prognosis in certain cancers. Current data thus suggest that the biological role of CRB3 in tumors is complex. Whether CRB3 acts as a tumor accelerator or suppressor may depend on the individual-specific, unique characteristics of tumor cells. Understanding these dual functions may contribute to the development of novel polarity-targeted therapeutic strategies for cancers of differing origin.
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    Direct Cryo-ET observation of platelet deformation induced by SARS-CoV-2 spike protein
    (Nature Research, 2023-02-04) Cyrus Kuhn, Christopher; Basnet, Nirakar; Bodakuntla, Satish; Alvarez-Brecht, Pelayo; Nichols, Scott; Martínez-Sánchez, Antonio; Agostini, Lorenzo; Soh, Young-Min; Takagi, Junichi; Biertümpfel, Christian; Mizuno, Naoko; Ingeniería de la Información y las Comunicaciones
    SARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic. Its high pathogenicity is due to SARS-CoV-2 spike protein (S protein) contacting host-cell receptors. A critical hallmark of COVID-19 is the occurrence of coagulopathies. Here, we report the direct observation of the interactions between S protein and platelets. Live imaging shows that the S protein triggers platelets to deform dynamically, in some cases, leading to their irreversible activation. Cellular cryo-electron tomography reveals dense decorations of S protein on the platelet surface, inducing filopodia formation. Hypothesizing that S protein binds to filopodia-inducing integrin receptors, we tested the binding to RGD motif-recognizing platelet integrins and find that S protein recognizes integrin αvβ3. Our results infer that the stochastic activation of platelets is due to weak interactions of S protein with integrin, which can attribute to the pathogenesis of COVID-19 and the occurrence of rare but severe coagulopathies.
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    Three-dimensional epithelial cultures: a tool to model cancer development and progression
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Eritja, Núria; Dolcet, Xavier; Matias-Guiu, Xavier
    Loss of cell polarity is a hallmark of cancer, and although this feature is commonly observed in advanced tumors; growing evidence indicates that loss of cell-cell adhesion and cell polarity may also be important in early stages of cancer. Despite recent important advances, much remains unclear about the molecular and biophysical mechanisms involved in phenotypic changes observed in epithelial architecture during carcinogenesis. Over the past decade the use of three dimensional cultures (3D) has emerged as a valuable tool to study the functions of cancer genes and pathways in an adequate polarized context. 3D cultures are an outstanding tool to understand the morphologic consequences of molecular alterations. In other words, 3D cultures allow a much better understanding of the pathological features of tumours, with the microscope. In this review we will focus on how 3D models have provided unique insights into how basic cell biological processes impact in higher-order tissue architecture and how these models have enhanced our understanding of carcinoma biology.