Tumors derived from inoculation of SHP2-depleted, but SHP2 growth–independent, mouse melanoma and colon carcinoma cell lines displayed a typically subverted architecture, in which proliferative tumor cells surrounding a remodeled vessel formed “vascular islands”, each limited by surrounding hypoxic and dead tumor tissue, where inflammatory blood cells were limited. Here, PTPN11 is linked to colon carcinoma.