Junctional complexes in epithelial cells: sentinels for extracellular insults and intracellular homeostasis

The cell-cell and cell-ECM junctions within the epithelial tissues are crucial anchoring structures that provide architectural stability, mechanical resistance, and permeability control. Their indispensable role as signaling hubs orchestrating cell shape-related changes such as proliferation, differentiation, migration, and apoptosis has also been well recognized. However, growing amount of evidence now suggests that the multitasking nature of epithelial junctions extends well beyond anchorage-dependent or cell shape change-related biological processes. In this review, we discuss the emerging roles of junctional complexes in regulating innate immune defense, stress resistance, and intracellular proteostasis of the epithelial cells, with emphasis on the upstream regulation of epithelial junctions on various aspects of the epithelial barrier.