Head and neck squamous cell carcinomas (HNSCCs) represent a diverse group of malignancies, both clinically and biologically, with human papillomavirus (HPV) infection playing a significant role. HPV-positive tumours generally tend to have a better prognosis and are driven by oncoproteins E6 and E7. In contrast, HPV-negative tumours typically have a worse prognosis and are often linked to mutations in tumour suppressor genes. HNSCCs exist within a complex environment known as the tumour microenvironment (TME). The TME includes tumour cells, cancer stem cells (CSCs), cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM), blood vessels, and various signalling molecules. These components support tumour progression, invasion, metastasis, and resistance to treatment. Intercellular signalling within the TME-mediated by cytokines such as IL-6, TGF-b, and galectins-further promotes tumour growth and systemic effects like cachexia. Notably, the TME shares features with granulation tissue during wound healing, supporting the concept of cancer as a chronic, non-resolving wound. Effective therapy must target not only tumour cells but also the dynamic TME.

• Keywords
• CAF, IL-6, cancer, cancer-associated fibroblast, extracellular matrix, head and neck squamous cell carcinoma, immunity, stroma, therapy, tumour microenvironment,
• MeSH
• Squamous Cell Carcinoma of Head and Neck * immunology   pathology   MeSH
• Cancer-Associated Fibroblasts immunology   pathology   MeSH
• Papillomavirus Infections immunology   complications   MeSH
• Humans MeSH
• Neoplastic Stem Cells immunology   pathology   MeSH
• Tumor Microenvironment * immunology   MeSH
• Head and Neck Neoplasms * immunology   pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The ability of cells to switch between different invasive modes during metastasis, also known as invasion plasticity, is an important characteristic of tumor cells that makes them able to resist treatment targeted to a particular invasion mode. Due to the rapid changes in cell morphology during the transition between mesenchymal and amoeboid invasion, it is evident that this process requires remodeling of the cytoskeleton. Although the role of the actin cytoskeleton in cell invasion and plasticity is already quite well described, the contribution of microtubules is not yet fully clarified. It is not easy to infer whether destabilization of microtubules leads to higher invasiveness or the opposite since the complex microtubular network acts differently in diverse invasive modes. While mesenchymal migration typically requires microtubules at the leading edge of migrating cells to stabilize protrusions and form adhesive structures, amoeboid invasion is possible even in the absence of long, stable microtubules, albeit there are also cases of amoeboid cells where microtubules contribute to effective migration. Moreover, complex crosstalk of microtubules with other cytoskeletal networks participates in invasion regulation. Altogether, microtubules play an important role in tumor cell plasticity and can be therefore targeted to affect not only cell proliferation but also invasive properties of migrating cells.

• Keywords
• 3D migration, amoeboid, cancer, invasion plasticity, mesenchymal, microtubules,
• Publication type
• Journal Article MeSH
• Review MeSH

The invasive behaviour of cancer cells underlies metastatic dissemination; however, due to the large plasticity of invasion modes, it is challenging to target. It is now widely accepted that various secreted cytokines modulate the tumour microenvironment and pro-inflammatory signalling can promote tumour progression. Here, we report that cells after mesenchymal-amoeboid transition show the increased expression of genes associated with the type I interferon response. Moreover, the sustained activation of type I interferon signalling in response to IFNβ mediated by the Stat1/Stat2/IRF9 complex enhances the round amoeboid phenotype in melanoma cells, whereas its downregulation by various approaches promotes the mesenchymal invasive phenotype. Overall, we demonstrate that interferon signalling is associated with the amoeboid phenotype of cancer cells and suggest a novel role of IFNβ in promoting cancer invasion plasticity, aside from its known role as a tumour suppressor.

• Keywords
• amoeboid, inflammation, interferon, invasion, melanoma, mesenchymal, plasticity,
• Publication type
• Journal Article MeSH

Stress fibers are actin bundles encompassing actin filaments, actin-crosslinking, and actin-associated proteins that represent the major contractile system in the cell. Different types of stress fibers assemble in adherent cells, and they are central to diverse cellular processes including establishment of the cell shape, morphogenesis, cell polarization, and migration. Stress fibers display specific cellular organization and localization, with ventral fibers present at the basal side, and dorsal fibers and transverse actin arcs rising at the cell front from the ventral to the dorsal side and toward the nucleus. Perinuclear actin cap fibers are a specific subtype of stress fibers that rise from the leading edge above the nucleus and terminate at the cell rear forming a dome-like structure. Perinuclear actin cap fibers are fixed at three points: both ends are anchored in focal adhesions, while the central part is physically attached to the nucleus and nuclear lamina through the linker of nucleoskeleton and cytoskeleton (LINC) complex. Here, we discuss recent work that provides new insights into the mechanism of assembly and the function of these actin stress fibers that directly link extracellular matrix and focal adhesions with the nuclear envelope.

• Keywords
• Dorsal fibers, Focal adhesions, LINC, Perinuclear actin cap, Stress fibers, α-Actinin,
• MeSH
• Actin Capping Proteins metabolism   MeSH
• Cell Nucleus metabolism   MeSH
• Mechanotransduction, Cellular physiology   MeSH
• Focal Adhesions physiology   MeSH
• Nuclear Envelope metabolism   MeSH
• Stress Fibers physiology   MeSH
• Humans MeSH
• Cell Movement physiology   MeSH
• Cell Polarity physiology   MeSH
• Cell Shape physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Actin Capping Proteins MeSH