Faculty Opinions recommendation of Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry.

Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial–mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotype.

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Biosynthesis of the cell adhesion molecule uvomorulin (E-cadherin) in Madin-Darby canine kidney epithelial cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)55045-6 ◽

1991 ◽

Vol 266 (29) ◽

pp. 19672-19680

Author(s):

E.M. Shore ◽

W.J. Nelson

Keyword(s):

Cell Adhesion ◽

Epithelial Cells ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Madin Darby Canine Kidney ◽

Kidney Epithelial Cells ◽

Darby Canine Kidney ◽

Canine Kidney ◽

E Cadherin

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T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

British Journal of Cancer ◽

10.1038/sj.bjc.6600597 ◽

2002 ◽

Vol 87 (9) ◽

pp. 1034-1041 ◽

Cited By ~ 21

Author(s):

J J French ◽

J Cresswell ◽

W K Wong ◽

K Seymour ◽

R M Charnley ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Adhesion ◽

T Cell ◽

Cancer Cells ◽

Pancreatic Cancer Cells ◽

E Cadherin ◽

T Cell Adhesion

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ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial–mesenchymal transition

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01540-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kejun Liu ◽

Xianwen Chen ◽

Ligang Wu ◽

Shiyuan Chen ◽

Nianxin Fang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Small Cell Lung Cancer ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition ◽

Egfr T790m ◽

E Cadherin

Abstract Background ID1 is associated with resistance to the first generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, the effect of ID1 expression on osimertinib resistance in EGFR T790M-positive NSCLC is not clear. Methods We established a drug-resistant cell line, H1975/OR, from the osimertinib-sensitive cell line H1975. Alterations in ID1 protein expression and Epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA levels. ID1 silencing and overexpression were used to investigate the effects of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess the proliferation rate in cells with altered of ID1 expression. Transwell assay was used to evaluate the invasion ability of different cells. The effects on the cell cycle and apoptosis were also compared using flow cytometry. Results In our study, we found that in osimertinib-resistant NSCLC cells, the expression level of the EMT-related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin were higher than those of sensitive cells. ID1 expression levels was closely related to E-cadherin and vimentin in both osimertinib-sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression in H1975/OR cells could inhibit cell proliferation, reduce cell invasion, promote cell apoptosis and arrested the cell cycle in the G1/G0 stage phase. Our study suggests that ID1 may induce EMT in EGFR T790M-positive NSCLC, which mediates drug resistance of osimertinib. Conclusions Our study revealed the mechanism of ID1 mediated resistance to osimertinib in EGFR T790M-positive NSCLC through EMT, which may provide new ideas and methods for the treatment of EGFR mutated NSCLC after osimertinib resistance.

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