Fig. 1.

Seed Factors, both seed intrinsic and extrinsic factors are depicted here. Seed extrinsic traits remodel the primary soil and secondary soil via tumor secreted factors, inducing ECM remodeling and hypoxia, and promoting formation of pre-metastatic niche. Seed intrinsic traits, including CSC, EMT-MET, Autophagy and metastatic dormancy, is in involved in cancer metastasis, EMT and autophagy are linked with stemness of CSCs. Two alternative means of generating CSCs are depicted here, intrinsic CSCs are thought to exist in primary tumors from the very early stages of tumorigenesis and induced CSCs may arise as a consequence of EMT. CSCs with metastatic potential would be the most tenacious “seed” invasion through surrounding tissues, and intravasation, as well as survival in circulation and the eventual colonization at distant sites