The potential of carbonic anhydrase enzymes as a novel target for anti-cancer treatment.

Carbonic anhydrase (CA) is a zinc-dependent metal enzyme that maintains the pH and carbon dioxide (CO2) homeostasis in cells by catalyzing the reversible hydration and dehydration of CO2 and bicarbonate (HCO3-). In mammals, there are 16 isozymes of CA existed, namely CAI to CAXIV, but only 15 isozymes are found in humans except CAXV. Human CAs have highly conserved catalytic domains, all of which are distributed in different tissues and play important physiological roles. Changes in their functions may disrupt the typical distribution of CAs throughout human body and therefore CAs can be used as diagnostic biomarkers for many diseases. Furthermore, the expression of CAs is correlated to the progression of numerous tumors, therapeutic sensitivity and patient prognosis. In this review, we discuss thoroughly the structure of CAs, their functional activities in human physiology, dysregulations and diseases related to CAs, and different types of CA inhibitors that can reverse their dysregulation.

Increased RUNX1 mutations in breast cancer disease progression.

Despite advances in screening, therapy and surveillance, breast cancer remains threatening to women. Worst, patients suffer from side effects of treatments and cancer cells become resistant. The emergence of RUNX1 in breast cancer has put it in a spotlight due to its roles in the disease progression. It also plays important roles in normal mammary glands such as for cell growth, proliferation, migration and stemness. However, mutations in the RUNX1 gene have changed the regulation of these phenotypes and the full spectrum of its implications in breast cancer patients is unknown. In this study therefore, the pattern of RUNX1 mutations in breast cancer patients was examined to understand its fundamental impacts on the disease. The perturbation of RUNX1 and its mutations in breast cancer was elucidated through different studies reported in cBioPortal in the past ten years. From our analyses, the majority of RUNX1 mutations were found in the primary breast cancer, with women constituted most of the mutations, especially on the left side of the breast. Similarly, increased number of mutations was observed in ER-positive breast cancer patients and this was also the case at the early stage of the disease development. The level of RUNX1 mutations also increased gradually as patients got older and the peak was highest in the patients of 60-70 years old. Altogether, these data indicated that the mutated RUNX1 gene contributed to the progression of breast cancer and understanding of its regulatory mechanisms is crucial to therapeutically target this gene in the future.

The CellProfiler pipeline analysis of cell migration.

We demonstrate herein a refined method to evaluate the migration capacity of monolayer cells using the CellProfiler pipeline. We used MDA-MB-231 cells, a triple-negative breast cancer cell line, as a model to perform the wound healing assay and proceeded with the pipeline analysis. In order to see a contrast in our analysis of cell migration, we treated the cells with 10 µM kartogenin for 48 h and compared the result to the control cells treated with 0.1 % dimethyl sulfoxide (DMSO). The migration rate of MDA-MB-231 cells could be measured precisely using this method whereby in the presence of 10 µM kartogenin, the cells migrated at 6.3 ± 1.7µmh-1 whilst the vehicle control migrated at 9.1 ± 3.2 µmh-1 (p < 0.05). The small changes in the rate of migration could be significantly differentiated and we believe that this method is accurate in analyzing data of scratch assays as it is of high precision and therefore can be used for high-throughput screenings.

RUNX1 as a Novel Molecular Target for Breast Cancer.

RUNX1 has long known for its role in hematopoiesis until recently it is implicated in human breast cancer pathogenesis. This has drawn attention in research as elevated expression of RUNX1 has been observed in invasive breast cancer, and mutations of the RUNX1 gene and its binding partner CBFß have been identified in luminal breast cancer patients, many of which have attributed to the development and progression of the disease. Increasing number of evidence also shows the involvement of RUNX1 in breast cancer migration and invasion that may lead to breast cancer metastasis. However, more studies need to be conducted to better understand its roles in these particular subtypes in breast cancer. This is important as evidence so far indicates that there are discrepancies with regards to the roles of RUNX1 in ER-positive and ER-negative breast cancer, both of which have posted a great challenge to recognize whether its deregulation is protecting or promoting breast cancer. This warrants further analysis to glean more information especially considering the perturbation of RUNX1 is mainly reported in ER-positive breast cancer. In this review, the roles of RUNX1 in breast cancer are discussed in a context dependent manner based on its involvement in the development and progression of the disease. The association of RUNX1 with other types of cancer is also included to emphasize a wider and possibly a different angle of involvement of RUNX1 in cancer.