Purpose: Triple-negative breast cancers (TNBC) are defined by a lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (ERBB2/HER2). Although initially responsive to chemotherapy, most recurrent TNBCs develop resistance, resulting in disease progression. Autophagy is a lysosome-mediated degradation and recycling process that can fu...

Autophagy, a "self-eating" cellular process, has dual roles in promoting and suppressing tumor growth, depending on cellular context. PTP4A3/PRL-3, a plasma membrane and endosomal phosphatase, promotes multiple oncogenic processes including cell proliferation, invasion, and cancer metastasis. In this study, we demonstrate that PTP4A3 accumulates in autophagosomes upon inhibition of autophagic d...

As current classical Hodgkin lymphoma (cHL) treatment strategies have pronounced side-effects, specific inhibition of signaling pathways may offer novel strategies in cHL therapy. Basal autophagy, a regulated catabolic pathway to degrade cell's own components, is in cancer linked with both, tumor suppression or promotion. The finding that basal autophagy enhances tumor cell survival would thus ...

BACKGROUND The clinical use of doxorubicin is limited by cardiotoxicity. Histopathological changes include interstitial myocardial fibrosis and the appearance of vacuolated cardiomyocytes. Whereas dysregulation of autophagy in the myocardium has been implicated in a variety of cardiovascular diseases, the role of autophagy in doxorubicin cardiomyopathy remains poorly defined. METHODS AND RESU...

Due to the involvement of macroautophagy/autophagy in different pathophysiological conditions such as infections, neurodegeneration and cancer, identification of novel small molecules that modulate the process is of current research and clinical interest. In this work, we developed a luciferase-based sensitive and robust kinetic high-throughput screen (HTS) of small molecules that modulate auto...

Accumulation of intracellular misfolded or damaged proteins is associated with both normal aging and late-onset degenerative diseases. Two cellular clearance mechanisms, the ubiquitin-proteasome system (UPS) and the macroautophagy/autophagy-lysosomal pathway, work in concert to degrade harmful protein aggregates and maintain protein homeostasis. Here we show that Mask, an Ankyrin-repeat and KH-...

Autophagy is an evolutionary conserved catabolic process activated in response to a variety of cellular stresses, for example nutrient deprivation or chemotherapy. During autophagy, cells engulf parts of their cytplasm in a double-membrane vesicle, where misfolded proteins or damaged organelles are degraded. A plethora of human diseases has been linked to autophagy, including cancer and neurode...

Many epithelial cancers, particularly gastrointestinal tract cancers, remain poor prognosis diseases, due to resistance to cytotoxic therapy and local or metastatic recurrence. We have previously shown that apoptosis incompetent esophageal cancer cells induce autophagy in response to chemotherapeutic agents and this can facilitate their recovery. However, known pharmacological inhibitors of aut...

Tight junction dysfunction plays a vital role in some chronic inflammatory diseases. Pro-inflammatory cytokines, especially tumor necrosis factor alpha (TNF-α), act as important factors in intestinal epithelial tight junction dysfunction during inflammatory conditions. Autophagy has also been shown to be crucial in tight junction function and claudin-2 expression, but whether autophagy has an e...

BACKGROUND A number of engineered nanoparticles induce autophagy, the main catabolic pathway that regulates bulk degradation of cytoplasmic material by the lysosomes. Depending on the specific physico-chemical properties of the nanomaterial, however, nanoparticle-induced autophagy may have different effects on cell physiology, ranging from enhanced autophagic degradation to blockage of autophag...