TY - JOUR
T1 - Functional and molecular characterization of the epithelioid to round transition in human colorectal cancer LoVo cells
AU - Debruyne, Philip R.
AU - Vermeulen, Stefan J.
AU - Berx, Geert
AU - Pocard, Marc
AU - Correia Da Rocha, Ana Sofia
AU - Li, Xuedong
AU - Cirnes, Luis
AU - Poupon, Marie France
AU - Van Roy, Frans M.
AU - Mareel, Marc M.
PY - 2003/10/16
Y1 - 2003/10/16
N2 - In subclones of the human colon cancer LoVo cell line, there is a reproducible spontaneous transition from an epithelioid (E) to a round (R) morphotype. The E to R transition is associated with increased cell growth, absence of E-cadherin-dependent compaction in a slow aggregation assay, loss of contact inhibition of motility and directional migration in a wound filling motility assay. Furthermore, none of the E subclones from LoVo was invasive into chick heart fragments. This is in contrast to the R subclones that were either nonadherent or adherent and invasive. Macroarray analysis demonstrated transcriptional downregulation of plakoglobin in R type LoVo cells and this was confirmed at the level of the mRNA by quantitative RT-PCR. Western blotting showed lower expression of all components of the E-cadherin/catenin complex in R subclones. Interestingly, treatment of R subclones with the demethylating agent 5-aza-2′-deoxycytidine resulted in restoration of the E morphotype, higher expression of E-cadherin, but not plakoglobin mRNA, and higher expression of E-cadherin and plakoglobin at the protein level.
AB - In subclones of the human colon cancer LoVo cell line, there is a reproducible spontaneous transition from an epithelioid (E) to a round (R) morphotype. The E to R transition is associated with increased cell growth, absence of E-cadherin-dependent compaction in a slow aggregation assay, loss of contact inhibition of motility and directional migration in a wound filling motility assay. Furthermore, none of the E subclones from LoVo was invasive into chick heart fragments. This is in contrast to the R subclones that were either nonadherent or adherent and invasive. Macroarray analysis demonstrated transcriptional downregulation of plakoglobin in R type LoVo cells and this was confirmed at the level of the mRNA by quantitative RT-PCR. Western blotting showed lower expression of all components of the E-cadherin/catenin complex in R subclones. Interestingly, treatment of R subclones with the demethylating agent 5-aza-2′-deoxycytidine resulted in restoration of the E morphotype, higher expression of E-cadherin, but not plakoglobin mRNA, and higher expression of E-cadherin and plakoglobin at the protein level.
KW - Colorectal cancer
KW - E-cadherin/catenin complex
KW - Invasion
KW - Morphotype
UR - http://www.scopus.com/inward/record.url?scp=0242690923&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1206628
DO - 10.1038/sj.onc.1206628
M3 - Article
C2 - 14562048
AN - SCOPUS:0242690923
SN - 0950-9232
VL - 22
SP - 7199
EP - 7208
JO - Oncogene
JF - Oncogene
IS - 46
ER -