Publikation:

FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth

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Datum

2002

Autor:innen

Hsia, Datsun A.
Puente, Xose S.
Cheresh, David A.
Schlaepfer, David D.

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The EMBO Journal. 2002, 21(23), pp. 6289-6302. eISSN 1460-2075. Available under: doi: 10.1093/emboj/cdf631

Zusammenfassung

Focal adhesion kinase (FAK) was first identified as a viral Src (v-Src) substrate, but the role of FAK in Src transformation events remains undefined. We show that stable expression of the FAK C-terminal domain (termed FRNK) in v-Src-transformed NIH 3T3 fibroblasts inhibited cell invasion through Matrigel and blocked experimental metastases in nude mice without effects on cell motility. FRNK inhibitory activity was dependent upon its focal contact localization. FRNK expression disrupted the formation of a v-Src-FAK signaling complex, inhibited p130Cas tyrosine phosphorylation, and attenuated v-Src-stimulated ERK and JNK kinase activation. However, FRNK did not affect v-Src-stimulated Akt activation, cell growth in soft agar, or subcutaneous tumor formation in nude mice. FRNK-expressing cells exhibited decreased matrix metalloproteinase-2 (MMP-2) mRNA levels and MMP-2 secretion. Transient FRNK expression in human 293 cells inhibited exogenous MMP-2 promoter activity and overexpression of wild-type but not catalytically-inactive (Ala-404) MMP-2 rescued v-Src-stimulated Matrigel invasion in the presence of FRNK. Our findings show the importance of FAK in Src-stimulated cell invasion and support a role for Src-FAK signaling associated with elevated tumor cell metastases.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

cell invasion, FAK, matrix, metalloproteinase, metastasis, Src

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ISO 690HAUCK, Christof R., Datsun A. HSIA, Xose S. PUENTE, David A. CHERESH, David D. SCHLAEPFER, 2002. FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. In: The EMBO Journal. 2002, 21(23), pp. 6289-6302. eISSN 1460-2075. Available under: doi: 10.1093/emboj/cdf631
BibTex
@article{Hauck2002block-7338,
  year={2002},
  doi={10.1093/emboj/cdf631},
  title={FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth},
  number={23},
  volume={21},
  journal={The EMBO Journal},
  pages={6289--6302},
  author={Hauck, Christof R. and Hsia, Datsun A. and Puente, Xose S. and Cheresh, David A. and Schlaepfer, David D.}
}
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