ABL Tyrosine Kinases promote HER2+ Breast Cancer Colonization of the Brain via Y-Box-Binding (YB-1) Protein-mediated translation of HER2

ABL tyrosine kinases promote colonization and outgrowth of metastatic breast cancer cells by activating not only transcriptional, but also translational programs. Human epidermal growth factor receptor 2-positive (HER2/ERBB2) breast cancer patients often present with brain metastasis. HER2-targeted therapies have not been successful to treat brain metastases in part due to poor blood-brain barrier (BBB) penetrance […]

Continue reading

ABL kinase-mediated regulation of lung epithelial injury and regeneration identifies new therapeutic strategies to treat pathogen-induced lung injury.

Damage to the lung epithelium by respiratory infections is associated with respiratory failure and may result in the induction of acute respiratory distress syndrome which has an incidence of about 200,000 cases in the United States each year and a mortality rate of 25-40%. We found that loss of Abl1 specifically in CC10 (also known […]

Continue reading

ABL-TAZ-AXL signaling axis regulates lung cancer metastasis to brain

Lung cancer is the leading cause of cancer mortality in the U.S., with an overall five-year survival rate of ~16%. Notably, lung cancer patients exhibit the highest prevalence of brain metastasis (40-60 %) among all cancer types. Brain metastases often result in functional impairment, cranial neuropathies, and increased mortality. Currently, there are no effective therapies […]

Continue reading

ABL Kinases Promote Breast Cancer Osteolytic Metastasis

Bone metastasis is a frequent complication of cancer, occurring in up to 70% of patients with advanced breast or prostate cancer. Breast cancer metastasis to the bone is associated with decreased survival, and patients with bone metastases experience severe pain, pathologic fractures, life-threatening hypercalcemia, spinal cord compression, and other nerve-compression syndromes. A greater understanding of […]

Continue reading

Inactivation of ABL Kinases Suppresses Lung Cancer Metastasis

Topic 2

Current therapies to treat non-small cell lung carcinoma (NSCLC) have proven ineffective due to transient, variable and incomplete responses. We found that ABL kinases, ABL1 and ABL2, promote metastasis of lung cancer cells harboring EGFR or KRAS mutations. Pharmacological inhibition (Figure 1) or knockdown of both ABL kinases suppresses NSCLC metastasis (Figure 2). ABL kinases […]

Continue reading

Regulation of Endothelial Cell Survival and Vascular Function by ABL Kinases

Topic 3

Disruption of vascular function is implicated in diverse pathological conditions and is often associated with aberrant angiogenesis and/or altered vascular barrier function. Angiogenesis and vascular function are regulated by the binding of diverse growth factors to their cognate receptor tyrosine kinases. Among these are the angiopoietins (Angpt), which activate the Tie2 receptor tyrosine kinase in […]

Continue reading

Regulation of Epithelial Cell Polarity by Arg and β1-Integrin Signaling Axis

Topic 4

Establishment and maintenance of epithelial cell polarity is regulated in part by signaling from adhesion receptors. Loss of cell polarity is associated with multiple pathologies including the initiation and progression of various cancers. The β1-integrin plays a role in the regulation of cell polarity. We identified a novel role for the Arg (Abl2) kinase in […]

Continue reading

Modulation of T cell-mediated Inflammation and Chemokine-induced Migration by an ABL-HEF1-Rap1 Signaling Axis

The identity of signaling mediators that link stimulation of chemokine receptors to pathways that promote T cell polarization and migration remains poorly understood. Chemokine signaling is essential for T lymphocyte trafficking during homeostasis and in response to inflammation. We have identified new roles for the Abl kinases in the regulation of chemokine-induced T cell migration […]

Continue reading

Abi1 is a Novel Target of α4β1 Integrin Signaling

Dynamic signals linking the actin cytoskeleton and cell adhesion receptors are essential for morphogenesis during development and normal tissue homeostasis. Abi1 is a central regulator of actin polymerization and a binding partner of the Abl kinases. The α4 integrin receptor is associated with enhanced protrusive activity and regulation of directional cell migration. Among integrin subunits, […]

Continue reading