CSC signaling activity or overactivation of pathways such as Wnt/RSPO (R-spondin) [27], c-Jun N-terminal protein kinase (JNK) [28], Nodal/Activin [29], Notch [30] or Hedgehog [24] as well as adaptability of CSCs to the ever-changing tumor microenvironment and CSC niche [31,32,33] are further critical components of the CSC concept. Here, RSPO1 is linked to neoplasm.