Abstract
Polo-like kinase 1 (PLK1) has important functions in maintaining genome stability via its role in mitosis. Because PLK1 is up-regulated in many invasive carcinomas, we asked whether it may also play a role in acquisition of invasiveness, a crucial step in transition to malignancy. In a model of metaplastic basal-like breast carcinoma progression, we found that PLK1 expression is necessary but not sufficient to induce invasiveness through laminin-rich extracellular matrix. PLK1 mediates invasion via vimentin and beta1 integrin, both of which are necessary. We observed that PLK1 phosphorylates vimentin on Ser82, which in turn regulates cell surface levels of beta1 integrin. We found PLK1 to be also highly expressed in preinvasive in situ carcinomas of the breast. These results support a role for the involvement of PLK1 in the invasion process and point to this pathway as a potential therapeutic target for preinvasive and invasive breast carcinoma treatment.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
Apoptosis / physiology
-
Blotting, Western
-
Breast Neoplasms / enzymology*
-
Breast Neoplasms / genetics
-
Breast Neoplasms / therapy
-
Carcinoma, Ductal, Breast / enzymology
-
Carcinoma, Ductal, Breast / pathology
-
Carcinoma, Intraductal, Noninfiltrating / enzymology
-
Carcinoma, Intraductal, Noninfiltrating / pathology
-
Cell Cycle Proteins / antagonists & inhibitors
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism*
-
Cell Movement
-
Collagen
-
Drug Combinations
-
Extracellular Matrix / enzymology*
-
Female
-
Humans
-
In Situ Nick-End Labeling
-
Integrin beta1 / metabolism
-
Laminin / metabolism
-
Mice
-
Mice, Inbred BALB C
-
Mice, Nude
-
Phosphorylation
-
Polo-Like Kinase 1
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism*
-
Proteoglycans
-
Proto-Oncogene Proteins / antagonists & inhibitors
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism*
-
RNA, Small Interfering / pharmacology
-
Vimentin / metabolism
Substances
-
Cell Cycle Proteins
-
Drug Combinations
-
Integrin beta1
-
Laminin
-
Proteoglycans
-
Proto-Oncogene Proteins
-
RNA, Small Interfering
-
Vimentin
-
matrigel
-
Collagen
-
Protein Serine-Threonine Kinases