Clumpy galaxies in the Galaxy Evolution from Morphology and SEDs and Great Observatories Origins Deep Survey fields are examined for clues to their evolution into modern spirals. The magnitudes of the clumps and the surface brightnesses of the interclump regions are measured and fitted to models of stellar age and mass. There is an evolutionary trend from clump clusters with no evident interclump emission to clump clusters with faint red disks, to spiral galaxies of the flocculent or grand design types. Along this sequence, the interclump surface density increases and the mass surface density contrast between the clumps and the interclump regions decreases, suggesting a gradual dispersal of clumps to form disks. Also along this sequence, the bulge-to-clump mass ratios and age ratios increase, suggesting a gradual formation of bulges. All of these morphological types occur in the same redshift range, indicating that the clump cluster morphology is not the result of bandshifting. This redshift range also includes clear examples of interacting galaxies with tidal tails and other characteristic features, indicating that clump clusters, which do not have these features, are not generally interacting. Comparisons to local galaxies with the same rest wavelength and spatial resolution show that clump clusters are unlike local flocculent and spiral galaxies primarily because of the high clump/interclump contrasts in the clump clusters. They bear a striking resemblance to local dwarf irregulars, however. This resemblance is consistent with a model in which the clumpy morphology comes from gravitational instabilities in gas with a high turbulent speed compared to the rotation speed and a high mass fraction compared to the stars. The morphology does not depend on galaxy mass as much as it depends on evolutionary stage: clump clusters are 100 times more massive than local dwarfs. The apparent lack of star formation in damped Lyman alpha absorbers may result from fast turbulence.

The purpose of this study was to determine the role of long-chain fatty acyl-CoA synthetase 4 (ACSL4) in breast cancer. Public databases were utilized to analyze the relationship between ACSL4 mRNA expression and the presence of steroid hormone and human epidermal growth factor receptor 2 (HER2) in both breast cancer cell lines and tissue samples. In addition, cell lines were utilized to assess the consequences of either increased or decreased levels of ACSL4 expression. Proliferation, migration, anchorage-independent growth and apoptosis were used as biological end points. Effects on mRNA expression and signal transduction pathways were also monitored. A meta-analysis of public gene expression databases indicated that ACSL4 expression is positively correlated with a unique subtype of triple negative breast cancer (TNBC), characterized by the absence of androgen receptor (AR) and therefore referred to as quadruple negative breast cancer (QNBC). Results of experiments in breast cancer cell lines suggest that simultaneous expression of ACSL4 and a receptor is associated with hormone resistance. Forced expression of ACSL4 in ACSL4-negative, estrogen receptor α (ER)-positive MCF-7 cells resulted in increased growth, invasion and anchorage independent growth, as well as a loss of dependence on estrogen that was accompanied by a reduction in the levels of steroid hormone receptors. Sensitivity to tamoxifen, triacsin C and etoposide was also attenuated. Similarly, when HER2-positive, ACSL4-negative, SKBr3 breast cancer cells were induced to express ACSL4, the proliferation rate increased and the apoptotic effect of lapatinib was reduced. The growth stimulatory effect of ACSL4 expression was also observed in vivo in nude mice when MCF-7 control and ACSL4-expressing cells were utilized to induce tumors. Our data strongly suggest that ACSL4 can serve as both a biomarker for, and mediator of, an aggressive breast cancer phenotype.