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A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f‐actin and β1‐integrin point contact distribution
Author(s) -
Aguirre Ghiso Julio A.,
Farías Eduardo F.,
Alonso Daniel F.,
Arregui Carlos,
Bal de Kier Joffé Elisa
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970529)71:5<881::aid-ijc29>3.0.co;2-9
Subject(s) - focal adhesion , phospholipase d , actin cytoskeleton , microbiology and biotechnology , protein kinase c , integrin , fibronectin , integrin linked kinase , cell growth , signal transduction , chemistry , biology , cell , protein kinase a , cytoskeleton , kinase , biochemistry , extracellular matrix , cyclin dependent kinase 2
Spreading is a critical process involved in motility and growth of tumor cells during the metastatic cascade. Focal adhesion kinase, src‐proteins and PKC have been reported to participate in the regulation of cytoskeleton organization in both normal and transformed cells during spreading. The role of other signaling enzymes such as PLD and PAP has not been studied during spreading in tumor cells. We now show that the spreading of murine mammary adenocarcinoma LM3 cells was significantly reduced by n‐butanol, a PLD and PKC inhibitor, with a maximal inhibition of 54% ( p <0.001) in both the presence and absence of serum, as measured by phase‐contrast microscopy. PMA only stimulated cell spreading over the control in the absence of serum and n‐butanol inhibition was completely reversed by PMA treatment in both conditions. PA, the product of PLD activity, stimulated LM3 cell spreading and the same effect was observed with staurosporine. Spreading was enhanced when cells were seeded on collagen‐IV‐ or fibronectin‐coated surfaces and n‐butanol could inhibit both integrin‐derived signals. Cell spreading inhibition correlated with the absence of f‐actin bundles and fewer β1‐integrin point contacts as determined by double immunofluorescence microscopy. In addition, n‐butanol inhibited the proliferation of LM3 cells in the presence of serum ( p <0.01). These results suggest that β1‐integrin and f‐actin/point contact assembly, involved in spreading and proliferation, require the participation of PLD‐PKC regulatory pathways in LM3 cells. Int. J. Cancer 71: 881‐890, 1997. © 1997 Wiley‐Liss Inc.