Fig. 1

The intracellular signaling of TSPANs in cancer. Although mainly located on cell membrane, TSPANs have no natural ligands. They affect different biological processes mainly via interacting with different partner molecules to form TEMs. Integrins are the most prominent partner of TSPANs. Other partners of TSPANs include growth factor receptors (EGFR [9], mtTGF-β [10]), transporters (ASCT2 [11], FATP1 [12], MDR1 [13]), membrane-linked kinases (BTRC [14], SOCSS3 [15], ATXN3 [16]), other transmembrane proteins (ADAM10[17], CD44 [18], p120 [19]). Thus, TSPANs can affect several signaling pathways, including PI3K/AKT, Wnt/β-catenin, ERK1/2, STAT3/5, Src, Notch pathways