Haploinsufficiency of PTEN in suppressing cell proliferation results in a spontaneous path on a downhill slope as PTEN levels decrease (a). Of note, this path toward PC is formed by a stable valley. Variable levels of LKB1 have little effect on normal prostate epithelial cells (b). After PTEN loss, there is a steep path for transdifferentiation from epithelial to squamous cancer (c). Partial loss of LKB1 will not suffice to escape from the epithelial valley. This gives rise to the concept of high LKB1 competence against transdifferentiation. Complete LKB1 deletion is required to push cells toward the squamous cancer lineage.