Peculiarities of Proliferation and Differentiation of Cambial and Daughter Cells of Epidermal-Dermal Morphofunctional Zone in Normal Epithelium and in Cancer

Abstract

The cambial and daughter cells of normal epithelium function in the morphofunctional zone consisting of two subunits with 12 cambial cells in each. Daughter cells are differentiated in an electrical field created by 12 pairs of maternal and daughter cells, products of division of cambial cells located in the same subunit. The differentiation requires relaxation of the cortex of daughter cells via expression of SH3 domain of Src kinase by dermal daughter cells, which leads to a decrease in activity of RhoA in epidermal cells, their stretching, and activation of SH2 domain of Src responsible for differentiation. Reduction of the number of cambial cells to 6 and, consequently, weakening of electrical field produced by them to a threshold value corresponding to very weak stretching of daughter epithelial cells results in a decrease in SH2 domain expression in these cells and its kinase contribution in Src. This leads to an increase in RhoA relative to Src, enhances cell contraction, impairs formation of stress fibrils and focal contacts, reduces cell flattening, and increases cell mobility. The decrease in the number of microtubules, intermediate filaments, and stress-fibrils changes the major cell axis direction, which, in turn, sharply reduces nucleus stretching and leads to impaired chromosome looping out near the centromeres and telomeres; the cells acquires signs of an epitheliocyte and a fibroblast, protein transcription is impaired, and daughter cells are transformed into malignant cell.

Epithelial tissue response to pathological effects in various age groups. Participation of morphofunctional zones and Src-kinase in this process

“…Along with this, compensatory mechanisms in the cell increase the thickness of the actin layer under the cell membrane, which is a barrier to the penetration of pathological agents. This is due to the fact that the prevalence of the inactive Src-kinase portion in the cell promotes the nucleation of actin from a new fixed point and the formation of a network of actin filaments, rather than long strands of stress fibers [26] . In this regard, the main actions of the virus are aimed at transforming the most part of the Src-kinase into the active form.…”