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Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis. By performing multiomic profiling, we recently uncovered super-enhancer heterogeneity between breast cancer subtypes. Our data also revealed TCOF1 as a putative TNBC-specific super-enhancer-regulated gene. TCOF1 plays a critical role in craniofacial development but its function in cancer remains unclear. Methods Overall survival and multivariant Cox regression analyses were conducted using the METABRIC data set. The effect of TCOF1 knockout on TNBC growth and stemness was evaluated by in vitro and in vivo assays. RNA-seq and rescue experiments were performed to explore the underlying mechanisms. Results TCOF1 is frequently upregulated in TNBC and its elevated expression correlates with shorter overall survival. TCOF1 depletion significantly inhibits the growth and stemness of basal-like TNBC, but not of mesenchymal-like cells, highlighting the distinct molecular dependency in different TNBC subgroups. RNA-seq uncovers several stem cell molecules regulated by TCOF1. We further demonstrate that KIT is a downstream effector of TCOF1 in mediating TNBC stemness. TCOF1 expression in TNBC is regulated by the predicted super-enhancer. Conclusions TCOF1 depletion potently attenuates the growth and stemness of basal-like TNBC. Expression of TCOF1 may serve as a TNBC prognostic marker and a therapeutic target.

Kinetics of phase transformations controlled by the diffusion of solute atoms has been studied by using a newly developed method based on probability theory. It is demonstrated that an exact solution considering the redistribution of the solute atoms can be achieved for a homogeneous one-dimensional system with all nuclei simultaneously generated at the beginning of the transformation. If the growth rate of the individual grains is not strongly correlated and obeys the square-root rule up to the very late stage, the equation describing the rate of the transformation as a function of time can be derived. The effect of the overlapping diffusion zones is discussed by numerically solving the diffusion function for the model systems. It can be concluded that the ''soft impingement,'' which is frequently argued in the works on the diffusion-controlled reaction, plays a role only in the final stage of the transformation and generally cannot cause bending of the curve in the Avrami-type plots.

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