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Activation of protein kinase C modulates cell-cell and cell-substratum adhesion of a human colorectal carcinoma cell line and restores 'normal' epithelial morphology.

Abstract：

:Abnormal cell adhesion is an important contributing factor in invasion and metastasis. Here, we show that morphologically 'normal' cell-cell and cell-substratum adhesion can be restored to a poorly differentiated carcinoma cell line by activation of protein kinase C (PKC). This cell line, VACO 10MS, grows as multicellular aggregates loosely attached to the substratum. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, 7.5 nM) induces rapid adhesive changes with 2 components. First, within 15 min of TPA the cells become closely apposed, an event resembling the 'compaction' seen in the mouse early embryo. Next, over 2 hr, the cells spread, forming a monolayer. We show that compaction depends on extracellular calcium, E-cadherin-mediated adhesion and F-actin but not on protein synthesis, microtubules or substratum adhesion. By contrast, cell spreading is independent of cadherin and extracellular Ca2+ but involves the formation of focal contacts containing alpkha(v) integrin. TPA treatment causes rapid translocation of PKC-alpha to the insoluble fraction. During compaction, actin- and PKC-alpha-containing lamellae form over the entire aggregate surface, those adjacent to the substratum appearing to initiate spreading. Compaction does not involve increased phosphorylation of the cadherin/catenin complex. We conclude that activation of PKC-alpha restores 'normal' morphology to these poorly differentiated cells. Our results are of general interest in relation to the regulation of cell adhesion and, through further investigation, may lead to identification of novel targets for therapeutic suppression of invasion and metastasis.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Cowell HE,Garrod DR

doi

10.1002/(sici)1097-0215(19990129)80:3<455::aid-ijc

subject

Has Abstract

pub_date

1999-01-29 00:00:00

pages

455-64

issue

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19990129)80:3<455::AID-IJC

journal_volume

pub_type

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Activation of protein kinase C modulates cell-cell and cell-substratum adhesion of a human colorectal carcinoma cell line and restores 'normal' epithelial morphology.