Cooperation of actin-sequestering protein, thymosin β-4 and hypoxia inducible factor-1α in tumor cell migration.
Cell migration plays an important role in many physiological and pathological processes, including tumor metastasis. Tumor cell migration is increased through the sequential induction of HIF-1α and VEGF under hypoxic conditions. Thymosin β-4 (Tβ4) is an actin-sequestering protein which controls cytoskeletal reorganization. Here, we investigated whether tumor cell migration could be co-operatively controlled by hypoxia and Tβ4. Cell migration was measured by wound healing assay with scratching confluent monolayers of tumor cells. Cell migration was enhanced 18 h after scratching cells. In addition, we found that the expression of HIF-1α, VEGF-A isoform 164/120 and Tβ4 was increased by scratching cells. Cell migration was decreased by the inhibition of Tβ4 or HIF-1α expression with lentiviral shRNA of Tβ4 or siRNA of HIF-1α, respectively. In contrast, cell migration was increased by the treatment with Tβ4 proteins. The inhibitory effect of Tβ4-shRNA or HIF-1α-siRNA was also attenuated by treatment with Tβ4 proteins. Collectively, these findings suggest that Tβ4 and HIF-1α cooperatively enhance tumor cell migration.
Ryu
Yun-Kyoung
YK
Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea.
Im
Yun-Sun
YS
Moon
Eun-Yi
EY
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D013947:Thymosin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000099201:Thymosin beta(4)
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D013947:Thymosin; D000099201:Thymosin beta(4)