When barriers break: Epithelial integrity and adhesion signaling in squamous cell carcinoma

Scope:This Research Topic explores how disruption of epithelial integrity drives the initiation, progression, and treatment response of squamous cell carcinoma (SCC) across stratified epithelia, including the skin, head and neck, esophagus, cervix, and lung. The collection will focus on how the breakdown of cell–cell junctions, epithelial polarity, and tissue architecture reshapes tumor behavior, promotes local invasion, and supports malignant progression in SCC.Rather than addressing adhesion signaling in cancer in broad terms, this topic is centered on the epithelial barrier as a functional tumor suppressor system and on the consequences of its failure in squamous malignancies. We welcome studies that examine how alterations in adherens junctions, desmosomes, tight junctions, hemidesmosomes, and polarity complexes contribute to epithelial transformation, collective behavior, plasticity, and resistance to therapy in SCC models and patient derived settings.We invite Original Research, Reviews, Mini Reviews, Perspectives, and Methods articles addressing, but not limited to, the following themes:Remodeling and dysfunction of adherens junctions, desmosomes, tight junctions, and hemidesmosomes during squamous carcinogenesisEpithelial polarity regulators such as Scribble, Par, and Crumbs in tissue organization and SCC developmentLoss of epithelial cohesion, partial EMT, collective invasion, and cellular plasticity in SCC progressionInterplay between junctional architecture and oncogenic signaling pathways relevant to SCC, including Hippo/YAP-TAZ, Wnt/β-catenin, Src family signaling, and Rho GTPase-regulated cytoskeletal programsCell matrix interactions and basement membrane remodeling as contributors to invasive transition in squamous tumorsStromal, inflammatory, and immune cues that destabilize epithelial organization or exploit adhesion defects in SCCTissue specific and shared mechanisms of epithelial breakdown across cutaneous, head and neck, esophageal, cervical, and pulmonary SCCBiomarkers and therapeutic strategies aimed at restoring epithelial organization or targeting vulnerabilities created by barrier failureAbstract:Squamous cell carcinomas (SCCs) arise in epithelial tissues that depend on strong intercellular adhesion, apicobasal polarity, and organized barrier function to maintain homeostasis. Across SCC subtypes of the skin, head and neck, esophagus, cervix, and lung, one of the clearest features of malignant progression is the gradual breakdown of this epithelial order. Junctional disassembly, polarity loss, and altered interactions with the surrounding matrix do not simply accompany tumor progression; they help drive the shift from controlled epithelial renewal to invasive and therapy refractory disease.In stratified epithelia, structures such as adherens junctions, desmosomes, tight junctions, and hemidesmosomes coordinate tissue cohesion, differentiation, and mechanical resilience. Their disruption can reprogram signaling networks that regulate growth, survival, migration, and cell-state plasticity. At the same time, loss of polarity regulators such as Scribble, Par, and Crumbs further weakens tissue architecture and promotes tumor permissive behavior. In SCC, these events are tightly linked to local invasion, collective migration, abnormal differentiation, and heterogeneous responses to therapy.This Research Topic aims to bring together multidisciplinary work on the role of epithelial barrier failure, junctional remodeling, and polarity deregulation in squamous cell carcinoma. We especially encourage contributions that connect epithelial architecture to tumor progression across SCC subtypes, clarify how adhesion defects shape communication with stromal and immune compartments, and identify biomarkers or therapeutic opportunities linked to the loss of epithelial integrity. By focusing on SCC as a disease of disrupted epithelial organization, this collection seeks to define how breakdown of tissue cohesion creates both biological insight and translational opportunity. Topic editors: Cristina Porcheri, Guya Diletta Marconi Source: https://www.frontiersin.org/research-topics/82550/when-barriers-break-epithelial-integrity-and-adhesion-signaling-in-squamous-cell-carcinoma