Title: Regulation of Inflammatory Breast Cancer Cell Invasion through Akt1/PKBα Phosphorylation of RhoC GTPase
Authors: Lehman, Heather L ×
Van Laere, Steven
van Golen, Cynthia M
Vermeulen, Peter B
Dirix, Luc Y
van Golen, Kenneth L #
Issue Date: Oct-2012
Publisher: American Association for Cancer Research
Series Title: Molecular Cancer Research vol:10 issue:10 pages:1306-1318
Abstract: With a 42% and 18% 5- and 10-year respective disease-free survival rate, inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer. IBC invades the dermal lymphatic vessels of the skin overlying the breast and as a consequence nearly all women have lymph node involvement and ∼1/3 have gross distant metastases at the time of diagnosis. One year after diagnosis ∼90% of patients have detectable metastases, making IBC a paradigm for lymphovascular invasion. Understanding the underlying mechanisms of the IBC metastatic phenotype is essential for new therapies. Work from our laboratory and others show distinct molecular differences between IBC and non-IBCs (nIBCs). Previously we showed that RhoC GTPase is a metastatic switch responsible for the invasive phenotype of IBC. In this study we integrate observations made in IBC patients with in vitro analysis. We show that the PI3K/Akt signaling pathway is crucial in IBC invasion. Key molecules involved in cytoskeletal control and cell motility are specifically upregulated in IBC patients compared with stage and cell-type-of-origin matched nIBCs patients. Distinctively, RhoC GTPase is a substrate for Akt1 and its phosphorylation is absolutely essential for IBC cell invasion. Further our data show that Akt3, not Akt1 has a role in IBC cell survival. Together our data show a unique and targetable pathway for IBC invasion and survival. Mol Cancer Res; 10(10); 1306-18. ©2012 AACR.
ISSN: 1541-7786
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
× corresponding author
# (joint) last author

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