Type: Primary Research article
Title: Proteomic Characterization of Aromatase Inhibitor Resistant Breast Cancer Cells Reveal the Presence of a Novel Nuclear Chaperone
Authors: Karen Gallegos Villalobos1, Jankiben Patel1, Shawn Llopis2, Rashidra R. Walker1, A. Michael Davidson1, Wensheng Zhang3, Kun Zhang3, Syreeta L. Tilghman1
Affiliations: 1Florida A&M University, Division of Basic Sciences, College of Pharmacy, 1415 S. Martin L. King Jr. Blvd, Tallahassee, FL 32307;
2Xavier University of Louisiana, Division of Basic Pharmaceutical Sciences, College of Pharmacy, 1 Drexel Dr., New Orleans, LA 70125;
3Xavier University of Louisiana, Division of Mathematical and Physical Sciences, Department of Computer Science, College of Arts and Sciences, 1 Drexel Dr., New Orleans, LA 70125
Abstract: To understand the mechanisms associated with aromatase inhibitor resistance, a global proteomic analysis was conducted on letrozole resistant breast cancer cells (LTLT-Ca) cultured in suspension as mammospheres and compared to their adherent counterparts. Results demonstrated that LTLT-Ca mammospheres displayed a 35-fold increase in midasin protein expression which correlated to decreased relapse-free survival in ER breast cancer patients. Moreover, midasin protein is ubiquitously expressed in normal tissue, but overexpressed in breast carcinoma tissue and cell lines. Taken together, our results demonstrate that midasin overexpression is positively associated with aromatase inhibitor-resistant breast cancer.
Title: Hormonal and adipose profile of breast cancer patients and metastatic dormancy dynamics
Authors: Danila Coradini1, Romano Demicheli2, Elia Biganzoli1,2
Affiliations: 1Laboratory of Medical Statistics and Epidemiology,“Giulio A. Maccacaro”, Department of Clinical Sciences and Community Health, University of Milan, Via Vanzetti 5, 20133 Milan, Italy.
2Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan Campus Cascina Rosa, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy.
Abstract: Breast cancer is the commonest cancer and leading cause of cancer death in women worldwide, with an estimated 1.7 million cases and over 520,000 deaths in 2012, accounting for 25% of all female cancers and 15% of all female cancer deaths due to distant metastasis. Understanding how the hormonal and adipose profile of breast cancer patients affect the metastatic dormancy dynamics is of paramount importance to prevent distant metastasis awake and spread, and ameliorate the effects of the adjuvant treatment.
Title: Cell plasticity and prostate cancer: the role of Epithelial-Mesenchymal Transition (EMT) in tumor progression, invasion, metastasis and cancer therapy resistance
Authors: S. Papanikolaou, K. Gyftopoulos
Affiliations: Department of Anatomy, University of Patras Medical School, Patras, Greece
Abstract: Prostate cancer, the second most common cancer in men, is characterized by high heterogeneity that poses several therapeutic challenges. Recent data for many tumors, including prostate carcinoma, suggest that EMT, a dynamic, reversible cellular program which is a major event in embryonic morphogenesis, wound healing and cancer metastasis, may play a key role for tumor progression, invasion, metastasis and even resistance to therapy. In this review we describe the underlying mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to shed light on this complex cellular process.
Title: Epithelial-mesenchymal transition (EMT): a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance
Authors: Ahmad R. Safa
Affiliations: Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Abstract: Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with activation of an epithelial‐to‐mesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell‐to‐cell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer‐initiating cells in pancreatic tumors. PCSCs may represent subpopulations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen (ESA) as well as the drug transporter ABCG2, and grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between cancer stem cells (CSC) and EMT. In this review, I summarize the current understanding of the EMT mechanism, PDAC heterogeneity, links between EMT and CSCs, and potential therapeutic strategies to prevent EMT and trigger CSC growth inhibition and cell death.