Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro.
Experimental evidence supports a role for E-cadherin in suppressing invasion, metastasis, and proliferation. Germline mutations of the E-cadherin represent the genetic cause of hereditary diffuse gastric cancer (HDGC). In this type of tumor, isolated cancer cells permeate the basal membrane and paradoxically survive in the gastric wall in the absence of contact with neighbor epithelial cells or with the extracellular matrix. This suggests that upon E-cadherin deregulation, cells acquired resistance to apoptosis. To test this hypothesis, CHO cells stably expressing either wild-type E-cadherin or the HDGC-related germline mutations T340A and V832M were seeded either on a thin layer of collagen type I or on plastic and then subjected to the apoptotic agent taxol. We found that in vitro functional E-cadherin renders cells more sensitive to the effect of taxol. Our results also indicate that this effect is associated to decreased level of the anti-apoptotic bcl-2 protein.
Ferreira
Paulo
P
Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200 Porto, Portugal.
Oliveira
Maria José
MJ
Beraldi
Eliana
E
Mateus
Ana Rita
AR
Nakajima
Takashi
T
Gleave
Martin
M
Yokota
Jun
J
Carneiro
Fátima
F
Huntsman
David
D
Seruca
Raquel
R
Suriano
Gianpaolo
G
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016466:CHO Cells / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D005434:Flow Cytometry; D005562:Formazans / Q000494:pharmacology; D009154:Mutation; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D014162:Transfection
D015820:Cadherins; D005562:Formazans; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; C079782:MTT formazan; D017239:Paclitaxel