TY - JOUR
T1 - Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer
AU - Sun, Yue
AU - Turbin, Dmitry A.
AU - Ling, Kun
AU - Thapa, Narendra
AU - Leung, Samuel
AU - Huntsman, David G.
AU - Anderson, Richard A.
N1 - Funding Information:
This work was funded by NIH grants GM057549 and CA104708.
PY - 2010/1/14
Y1 - 2010/1/14
N2 - Introduction: The loss of E-cadherin based cell-cell contacts and tumor cell migration to the vasculature and lymphatic system are hallmarks of metastasis of epithelial cancers. Type I gamma phosphatidylinositol phosphate kinase (PIPKIγ), an enzyme that generates phosphatidylinositol 4,5-bisphosphate (PI4,5P2) a lipid messenger and precursor to many additional second messengers, was found to regulate E-cadherin cell-cell contacts and growth factor-stimulated directional cell migration, indicating that PIPKIγ regulates key steps in metastasis. Here, we assess the expression of PIPKIγ in breast cancers and have shown that expression correlated with disease progression and outcome.Methods: Using a tissue microarray, we analyzed 438 breast carcinomas for the levels of PIPKIγ and investigated the correlation of PIPKIγ expression with patient survival via Kaplan-Meier survival analysis. Moreover, via knockdown of the expression of PIPKIγ in cultured breast cancer cells with siRNA, the roles of PIPKIγ in breast cancer migration, invasion, and proliferation were examined.Results: Tissue microarray data shows that ~18% of the cohort immunostained showed high expression of PIPKIγ. The Kaplan-Meier survival analysis revealed a significant inverse correlation between strong PIPKIγ expression and overall patient survival. Expression of PIPKIγ correlated positively with epidermal growth factor receptor (EGFR) expression, which regulates breast cancer progression and metastasis. In cultured breast cancer cells, PIPKIγ is required for growth factor stimulated migration, invasion, and proliferation of cells.Conclusions: The results reveal a significant correlation between PIPKIγ expression and the progression of breast cancer. This is consistent with PIPKIγ 's role in breast cancer cell migration, invasion, and proliferation.
AB - Introduction: The loss of E-cadherin based cell-cell contacts and tumor cell migration to the vasculature and lymphatic system are hallmarks of metastasis of epithelial cancers. Type I gamma phosphatidylinositol phosphate kinase (PIPKIγ), an enzyme that generates phosphatidylinositol 4,5-bisphosphate (PI4,5P2) a lipid messenger and precursor to many additional second messengers, was found to regulate E-cadherin cell-cell contacts and growth factor-stimulated directional cell migration, indicating that PIPKIγ regulates key steps in metastasis. Here, we assess the expression of PIPKIγ in breast cancers and have shown that expression correlated with disease progression and outcome.Methods: Using a tissue microarray, we analyzed 438 breast carcinomas for the levels of PIPKIγ and investigated the correlation of PIPKIγ expression with patient survival via Kaplan-Meier survival analysis. Moreover, via knockdown of the expression of PIPKIγ in cultured breast cancer cells with siRNA, the roles of PIPKIγ in breast cancer migration, invasion, and proliferation were examined.Results: Tissue microarray data shows that ~18% of the cohort immunostained showed high expression of PIPKIγ. The Kaplan-Meier survival analysis revealed a significant inverse correlation between strong PIPKIγ expression and overall patient survival. Expression of PIPKIγ correlated positively with epidermal growth factor receptor (EGFR) expression, which regulates breast cancer progression and metastasis. In cultured breast cancer cells, PIPKIγ is required for growth factor stimulated migration, invasion, and proliferation of cells.Conclusions: The results reveal a significant correlation between PIPKIγ expression and the progression of breast cancer. This is consistent with PIPKIγ 's role in breast cancer cell migration, invasion, and proliferation.
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U2 - 10.1186/bcr2471
DO - 10.1186/bcr2471
M3 - Article
C2 - 20074374
AN - SCOPUS:77956037099
SN - 1465-5411
VL - 12
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - R6
ER -