Rho activation drives luminal collapse and eversion in epithelial acini Institutional Repository Document uri icon


  • AbstractEpithelial cells lining a gland and cells grown in a soft extracellular matrix polarize with apical proteins exposed to the lumen and basal proteins in contact with the extracellular matrix. Alterations to polarity, including an apical-out polarity, occur in human cancers. While some aberrant polarity states may result from altered protein trafficking, recent observations of an extraordinary tissue-level inside-out unfolding suggest an alternate pathway for altered polarity. Because mechanical alterations are common in human cancer including an upregulation of RhoA mediated actomyosin tension in acinar epithelia, we explored whether perturbing mechanical homeostasis could cause apical-out eversion. Acinar eversion was robustly induced by direct activation of RhoA in normal and tumor epithelial acini, or indirect activation of RhoA through blockage of 1 integrins, disruption of the LINC complex, oncogenic Ras activation, or Rac1 inhibition. Furthermore, laser ablation of a portion of the untreated acinus was sufficient to induce eversion. Analyses of acini revealed high curvature and low phosphorylated myosin in the apical cell surfaces relative to the basal surfaces. A vertex-based mathematical model which balances tension at cell-cell interfaces revealed a five-fold greater basal cell surface tension relative to the apical cell surface tension. The model suggests that the difference in surface energy between the apical and basal surfaces is the driving force for acinar eversion. Our findings raise the possibility that a loss of mechanical homeostasis may cause apical-out polarity states in human cancers.

altmetric score

  • 9.784

author list (cited authors)

  • Narayanan, V., Purkayastha, P., Yu, B. o., Pendyala, K., Chukkapalli, S., Cabe, J. I., ... Lele, T. P.

citation count

  • 0

complete list of authors

  • Narayanan, Vani||Purkayastha, Purboja||Yu, Bo||Pendyala, Kavya||Chukkapalli, Sasanka||Cabe, Jolene I||Dickinson, Richard B||Conway, Daniel E||Lele, Tanmay P

Book Title

  • bioRxiv

publication date

  • July 2022