Regulation of inflammatory breast cancer cell invasion through Akt1/PKBα phosphorylation of RhoC GTPase.

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.

Insulin-like growth factor-I receptor expression regulates neuroblastoma metastasis to bone.

Neuroblastoma is a pediatric tumor that preferentially metastasizes to bone. Patients with bone metastases have a mortality rate >93%, indicating a need for novel treatment targets. Our laboratory has shown that type I insulin-like growth factor receptor (IGF-IR) expression and activation regulate neuroblastoma cell proliferation, motility, invasion, and survival, and that expression of the IGF-IR correlates with neuroblastoma tumorigenicity.

RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility.

It is projected that in 2005, approximately 220 900 men will be newly diagnosed with carcinoma of the prostate (CaP). Men who are diagnosed with locally advanced or metastatic disease undergo androgen ablation therapy and most will relapse and progress within 18 months. Metastasis to bone is the major clinical concern during CaP progression, as it is associated with intractable pain, bone fracture and paralysis resulting from spinal cord compression.

Insulin-like growth factor I induces preferential degradation of insulin receptor substrate-2 through the phosphatidylinositol 3-kinase pathway in human neuroblastoma cells.

Insulin receptor substrate (IRS) signaling is regulated through serine/threonine phosphorylation, with subsequent IRS degradation. This study examines the differences in IRS-1 and IRS-2 degradation in human neuroblastoma cells. SH-EP cells are glial-like, express low levels of the type I IGF-I receptor (IGF-IR) and IRS-2 and high levels of IRS-1.

Differential regulation of insulin receptor substrate-1 degradation during mannitol and okadaic acid induced apoptosis in human neuroblastoma cells.

Insulin receptor substrate (IRS) proteins are major docking molecules for the type I insulin like growth factor (IGF) receptor (IGF-IR) and mediate their effects on downstream signaling molecules. In this report, we investigated IRS-1 regulation during apoptosis in human neuroblastoma SH-EP cells. Treatment of SH-EP cells with mannitol or okadaic acid (OA) induces apoptosis with the typical characteristics of anoikis.