The extracellular loop 2 of TM4SF5 inhibits integrin alpha2 on hepatocytes under collagen type I environment.
Four-transmembrane L6 family member 5 (TM4SF5) and its homolog L6, a tumor antigen, form a four-transmembrane L6 family. TM4SF5 expression causes uncontrolled cell proliferation and angiogenesis. Although other genuine transmembrane 4 superfamily (TM4SF) members co-operate with integrins for cell migration, roles of TM4SF5 in the cellular spreading and migration are unknown. Using hepatocarcinoma cell clones that ectopically express TM4SF5, we found that cross talks via an extracellular interaction between TM4SF5 and integrin alpha2 in collagen type I environment inhibited integrin alpha2 functions such as spreading on and migration toward collagen I, which were recovered by suppression of TM4SF5 or structural disturbance of its second extracellular loop using a peptide or mutagenesis. Altogether, the observations suggest that TM4SF5 in hepatocytes negatively regulates integrin alpha2 function via an interaction between the extracellular loop 2 of TM4SF5 and integrin alpha2 during cell spreading on and migration through collagen I environment.
Cancer Research Institute, College of Medicine, Cell Dynamics Research Center, Seoul, Korea.
Sin-Ae
SA
Lee
Young Mee
YM
Kim
Tae Kyoung
TK
Kwak
Hyeon Jung
HJ
Kim
Semi
S
Kim
Wonil
W
Ko
Sung-Hoon
SH
Kim
Ki Hun
KH
Park
Hyun Jeong
HJ
Kim
Moonjae
M
Cho
Jung Weon
JW
Lee
D000951:Antigens, Neoplasm / Q000378:metabolism; D002465:Cell Movement; D002999:Clone Cells; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020239:Receptor Cross-Talk
D000951:Antigens, Neoplasm; D024042:Collagen Type I; D039421:Integrin alpha2; D008565:Membrane Proteins; C111029:TM4SF5 protein, human