Signaling pathways in anchoring junctions of epithelial cells: cell-to-cell and cell-to-extracellular matrix interactions

Abstract

Epithelial cells form the epithelium, one of the basic tissues of the human body. These cells present specializations from tissue to tissue, determining different structures and functions. Tissues formed by epithelial cells are characterized by the few extracellular matrix found between adjacent cells. In this way, to preserve tissue integrity, cells have to stick to each other and have to maintain a strict communication with the environment via cell junctions. Signal transduction is the main way of cell communication, being vital for the regulation of cell survival and proliferation. In cell junctions, this communication occurs through cell adhesion molecules that promote cell-to-cell and cell-to-extracellular matrix adhesion, as well as, enable the flow of information to the inside and to the outside of the cell. These molecules include integrins and cadherins, among others. The impairment of cell signaling in epithelial junctions has been involved in several pathological processes that underlie the development of, for example, colorectal cancer. Thus, epithelial cell signaling mediators have been explored as potential therapeutic targets and efforts have been made to achieve a deeper understanding of molecular events that occur at cell junctions. In this review, we address the current knowledge on the main signaling events that take place in anchoring junctions of epithelial cells, focusing both on cell-to-cell and cell-to-matrix interactions. To conclude, we explore some relevant consequences from epithelial cell signaling impairment and demonstrate that the molecular mediators of the pathways analyzed may be putative therapeutic targets.

IGFBP-2/PTEN: A critical interaction for tumours and for general physiology?

“…Although the RGD sequence was only acquired in IGFBP-1 during mammaliam evolution it was present within IGFBP-2 from early vertebrate evolution indicating that it has been a long retained functional characteristic of IGFBP-2 [4]. The integrin receptors are critical for the anchorage of cells to the extracellular matrix (ECM) within tissues and hence for maintaining tissue architecture [5,6]. In solid tissue an important safeguard is imposed by linking normal cell functions and proliferation to appropriate cues from the ECM that are mediated by signals from attachment receptors such as the integrin receptors.…”

“…The integrin receptors interact with growth factor receptors in an ancillary and permissive manner to ensure that the signals for growth and survival occur in the appropriate setting and not inappropriately in detached cells. It has also become clear that integrin receptors serve many other roles in regulating cell functions and integrating cues from the surrounding ECM [5,6].…”

The transcriptome difference between colorectal tumor and normal tissues revealed by single-cell sequencing

“…The intestinal epithelium is composed of at least seven different cell types [11], the main function of which is the absorption of nutrients, toxins and drugs. Recent studies suggest that intestinal epithelial cells play an important role in maintaining the intestinal immune homeostasis [12], and the aberrant cell signaling in epithelial junctions has been reported to be associated with the development of colorectal cancer [13].…”

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities

“…Cell signaling pathways are the main pillars behind cell communication as they are essential for the regulation of cell proliferation and survival. Impairments in transduction pathways or cell signaling lead to various pathological conditions such as cancer [ 64 ]. Regulatory circuits and molecular machineries that govern cellular function and fate are mainly disrupted by oncogenic mutations, conferring tumor cells towards various traits that assist their malignant behavior.…”