Abstract
Calpain 2 Regulates Akt-FoxO-p27Kip1 Protein Signaling Pathway in Mammary Carcinoma
Highlights
Calpains are intracellular calcium-dependent proteases implicated in cancer
Knockdown of Calpain 2 Expression in Mouse Mammary Carcinoma AC2M2 Cells—Mouse mammary carcinoma AC2M2 cells were transduced with control lentiviruses or lentiviruses encoding shRNA directed against capn2, and clones were selected
We show that knockdown of calpain 2 correlates with reduced in vivo tumor growth in an orthotopic engraftment model of mammary tumorigenesis
Summary
Results: Calpain 2 knockdown in breast cancer cells correlated with reduced in vitro proliferation, migration, and in vivo tumorigenicity as well as reduced Akt activation, increased nuclear FoxO localization, and increased p27Kip expression. Calpain 2 deficiency correlated with reduced Akt activity, increased protein phosphatase 2A levels, derepression of FoxO3a, and enhanced expression of the p27Kip tumor suppressor. These observations argue that calpain 2 promotes tumor cell growth both in vitro and in vivo through the PI3K-Akt-FoxO-p27Kip signaling cascade. Biochemical analysis suggested that calpain 2 regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27Kip signaling axis
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