JWA regulates melanoma metastasis by integrin alphaVbeta3 signaling.
JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As(2)O(3)) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As(2)O(3) on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin alpha(V)beta(3) signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma.
Bai
J
J
Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Zhang
J
J
Wu
J
J
Shen
L
L
Zeng
J
J
Ding
J
J
Wu
Y
Y
Gong
Z
Z
Li
A
A
Xu
S
S
Zhou
J
J
Li
G
G
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008545:Melanoma / Q000503:physiopathology*; D026901:Membrane Transport Proteins; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000473:pathology*
C484566:ARL6IP5 protein, human; D006360:Heat-Shock Proteins; D039302:Integrin alphaVbeta3; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins