Using fibrosarcoma HT1080 cells stably expressing PTK7 and its mutant and truncated species, the structure of which corresponded to the major PTK7 digest fragments, we demonstrated that the full-length membrane 1–1070 PTK7, the N-terminal 1–694 soluble ectodomain fragment, and the C-terminal 622–1070 and 726–1070 fragments differentially regulate multiple genes and signaling pathways in our highly invasive cancer cell model. Here, PTK7 is linked to cancer.