**2.6 KRT14 positive cells are linked to LC with distinct gene expression profile**

Transcriptome analysis of the KRT14 expressing LCs in breast cancer by RNA sequencing identified 239 differentially expressed signatures between the KRT14+ LCs and the KRT14<sup>−</sup> FC population. Gene ontology (GO) analyses, revealed that the expression of genes encoding ECM proteins, intermediate filaments, cytoskeleton organisation, and cell adhesion were significantly elevated in LCs compared to the FC population [34]. Interestingly, this study demonstrated that the LC subset is not a fixed lineage, however, the mechanisms regulating the interconversion of LCs and FCs remains unclear [34]. Recent studies suggest that the behaviour of breast cancer LCs can be mediated by CD44 expression levels where a high level of expression induces a shift towards an invasive LC phenotype [84]. Sonzogni et al. showed that KRT14 expressing LCs have a significantly higher expression of genes involved in metastasis progression including metallothionein-2 (*Mt2*), glycoprotein nonmetastatic B (*Gpnmb*), and adhesion molecule Amigo2, and secrete significantly higher levels of the collagen VI subunit A (*Col6a1*) [51]. In bladder cancer, stem-like KRT14+ cells gave rise to differentiated cells and were shown to be necessary for epithelial layer establishment following tissue damage [49]. A summary of studies and pathways involved in LC function is provided in **Table 1**.
