Phenotypic heterogeneity drives differential disease outcome in a mouse model of triple negative breast cancer.

The triple negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and is an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically distinct cell populations within a tumor play a crucial role in chemoresistance, tumor progression and metastasis. An increased understanding of the molecular regulators of intratumoral heterogeneity is crucial to the development of effective therapeutic strategies in TNBC.

Targeting the Id1-Kif11 Axis in Triple-Negative Breast Cancer Using Combination Therapy.

The basic helix-loop-helix (bHLH) transcription factors inhibitor of differentiation 1 () and inhibitor of differentiation 3 (referred to as ) have an important role in maintaining the cancer stem cell (CSC) phenotype in the triple-negative breast cancer (TNBC) subtype. In this study, we aimed to understand the molecular mechanism underlying control of CSC phenotype and exploit it for therapeutic purposes. We used two different TNBC tumor models marked by either depletion or expression in order to identify targets using a combinatorial analysis of RNA sequencing and microarray data.

Id Proteins Promote a Cancer Stem Cell Phenotype in Mouse Models of Triple Negative Breast Cancer via Negative Regulation of Robo1.

Breast cancers display phenotypic and functional heterogeneity and several lines of evidence support the existence of cancer stem cells (CSCs) in certain breast cancers, a minor population of cells capable of tumor initiation and metastatic dissemination. Identifying factors that regulate the CSC phenotype is therefore important for developing strategies to treat metastatic disease. The Inhibitor of Differentiation Protein 1 (Id1) and its closely related family member Inhibitor of Differentiation 3 (Id3) (collectively termed Id) are expressed by a diversity of stem cells and are required for metastatic dissemination in experimental models of breast cancer.

Interplay between a cytosolic and a cell surface carbonic anhydrase in pH homeostasis and acid tolerance of .

parasites have evolved to endure the acidic phagolysosomal environment within host macrophages. How cells maintain near-neutral intracellular pH and proliferate in such a proton-rich mileu remains poorly understood. We report here that, in order to thrive in acidic conditions, relies on a cytosolic and a cell surface carbonic anhydrase, LmCA1 and LmCA2, respectively.

The role of cancer stem cells in tumor heterogeneity and resistance to therapy.

Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor.