Differential expression and prognostic relevance of autophagy-related markers ATG4B, GABARAP, and LC3B in breast cancer.

Purpose: Previous studies indicate that breast cancer molecular subtypes differ with respect to their dependency on autophagy, but our knowledge of the differential expression and prognostic significance of autophagy-related biomarkers in breast cancer is limited.

Methods: Immunohistochemistry (IHC) was performed on tissue microarrays from a large population of 3992 breast cancer patients divided into training and validation cohorts. Consensus staining scores were used to evaluate the expression levels of autophagy proteins LC3B, ATG4B, and GABARAP and determine the associations with clinicopathological variables and molecular biomarkers.

Diverse mechanisms of autophagy dysregulation and their therapeutic implications: does the shoe fit?

In its third edition, the Vancouver Autophagy Symposium presented a platform for vibrant discussion on the differential roles of macroautophagy/autophagy in disease. This one-day symposium was held at the BC Cancer Research Centre in Vancouver, BC, bringing together experts in cell biology, protein biochemistry and medicinal chemistry across several different disease models and model organisms. The Vancouver Autophagy Symposium featured 2 keynote speakers that are well known for their seminal contributions to autophagy research, Dr.

Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers.

Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge of the particular mechanisms and players involved in different steps of autophagy regulation led to the ongoing discovery of small molecule inhibitors designed to disrupt this highly orchestrated process.

Identification of breast cancer cell subtypes sensitive to ATG4B inhibition.

Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target.

Techniques for the Detection of Autophagy in Primary Mammalian Cells.

Autophagy is a lysosomal catabolic pathway responsible for the degradation of cytoplasmic constituents. Autophagy is primarily a survival pathway for recycling cellular material in times of nutrient starvation, and in response to hypoxia, endoplasmic reticulum stress, and other stresses, regulated through the mammalian target of rapamycin pathway. The proteasomal pathway is responsible for degradation of proteins, whereas autophagy can degrade cytoplasmic material in bulk, including whole organelles such as mitochondria (mitophagy), bacteria (xenophagy), or lipids (lipophagy).

Monitoring Autophagic Flux by Using Lysosomal Inhibitors and Western Blotting of Endogenous MAP1LC3B.

Assays that monitor autophagic flux, or degradative completion of autophagy, are crucial for the assessment of the dynamic autophagy process in a variety of systems. Such assays help to distinguish between an increase in autophagosomes resulting from induced autophagic activity versus an increase in autophagosomes due to reduced lysosomal turnover. The majority of flux assays use autophagy protein MAP1LC3B (microtubule-associated proteins 1A/1B light chain 3B, here referred to as LC3B) as a marker for autophagy, and most are based on the use of reporters.

Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and -resistant triple-negative breast cancer.

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 function as an adaptive survival response during chemotherapy and contribute to chemoresistance.

Autophagy: from structure to metabolism to therapeutic regulation.

Multidisciplinary approaches are increasingly being used to elucidate the role of autophagy in health and disease and to harness it for therapeutic purposes. The broad range of topics included in the program of the Vancouver Autophagy Symposium (VAS) 2013 illustrated this multidisciplinarity: structural biology of Atg proteins, mechanisms of selective autophagy, in silico drug design targeting ATG proteins, strategies for drug screening, autophagy-metabolism interplay, and therapeutic approaches to modulate autophagy. VAS 2013 took place at the British Columbia Cancer Research Centre, and was hosted by the CIHR Team in Investigating Autophagy Proteins as Molecular Targets for Cancer Treatment.

Here, there be dragons: charting autophagy-related alterations in human tumors.

Macroautophagy (or autophagy) is a catabolic cellular process that is both homeostatic and stress adaptive. Normal cells rely on basal levels of autophagy to maintain cellular integrity (via turnover of long-lived proteins and damaged organelles) and increased levels of autophagy to buoy cell survival during various metabolic stresses (via nutrient and energy provision through lysosomal degradation of cytoplasmic components). Autophagy can function in both tumor suppression and tumor progression, and is under investigation in clinical trials as a novel target for anticancer therapy.