RESUMEN
Cancer progression requires the acquisition of mechanisms that support proliferative potential and metastatic capacity. MNRR1 (also CHCHD2, PARK22, AAG10) is a bi-organellar protein that in the mitochondria can bind to Bcl-xL to enhance its anti-apoptotic function, or to respiratory chain complex IV (COX IV) to increase mitochondrial respiration. In the nucleus, it can act as a transcription factor and promote the expression of genes involved in mitochondrial biogenesis, migration, and cellular stress response. Given that MNRR1 can regulate both apoptosis and mitochondrial respiration, as well as migration, we hypothesize that it can modulate metastatic spread. Using ovarian cancer models, we show heterogeneous protein expression levels of MNRR1 across samples tested and cell-dependent control of its stability and binding partners. In addition to its anti-apoptotic and bioenergetic functions, MNRR1 is both necessary and sufficient for a focal adhesion and ECM repertoire that can support spheroid formation. Its ectopic expression is sufficient to induce the adhesive glycoprotein THBS4 and the type 1 collagen, COL1A1. Conversely, its deletion leads to significant downregulation of these genes. Furthermore, loss of MNRR1 leads to delay in tumor growth, curtailed carcinomatosis, and improved survival in a syngeneic ovarian cancer mouse model. These results suggest targeting MNRR1 may improve survival in ovarian cancer patients.
RESUMEN
An aptamer-based colorimetric lateral flow assay was developed for the detection of human epidermal growth factor receptor 2 (HER2). In this study, two approaches were examined using HER2 binding aptamers and gold nanoparticles. The first method used was a solution-based adsorption-desorption colorimetric approach wherein aptamers were adsorbed onto the gold nanoparticle surface. Upon the addition of HER2, HER2 binds specifically with its aptamer, releasing the gold nanoparticles. Addition of NaCl then induces the formation of gold nanoparticle aggregates. This leads to a color change from red to blue and a detection limit of 10â¯nM was achieved. The second method used an adsorption-desorption colorimetric lateral flow assay approach wherein biotin-modified aptamers were adsorbed onto the gold nanoparticle surface in the absence of HER2. In the presence of HER2, HER2 specifically binds with its aptamer leading to release of the gold nanoparticles. These solutions were applied to the lateral flow assay format and a detection limit of 20â¯nM was achieved. Both colorimetric and lateral flow assays are inexpensive, simple, rapid to perform and produce results visible to the naked-eye.
