TPM3-ALK expression induces changes in cytoskeleton organisation and confers higher metastatic capacities than other ALK fusion proteins.
Translocations of the anaplastic lymphoma kinase (ALK) gene result in the production of a number of oncogenic ALK fusion proteins implicated in tumour development. We have previously shown that X-ALK fusion proteins have differential effects on the proliferation, transformation, and invasion properties of NIH3T3 cells in vitro. In the present study, we have investigated the metastatic potential of various X-ALK expressing cell lines using an experimental lung metastasis assay. We have shown that TPM3-ALK expression bestows higher metastatic capacities than other X-ALK fusion proteins and in addition, that TPM3-ALK fusion protein expression specifically induces changes in cell morphology and cytoskeleton organisation. Co-immunoprecipitation studies demonstrate a specific interaction between TPM3-ALK and endogenous tropomyosin. Together the specific actions of TPM3-ALK on the cytoskeleton organisation offer an interesting hypothesis with respect to the higher cell motility and metastatic potential of this fusion protein.
Armstrong
Florence
F
INSERM U563, Centre de Physiopathologie de Toulouse-Purpan, Department of Oncogenesis and Signalling in Haematopoietic Cells, Toulouse, France.
Lamant
Laurence
L
Hieblot
Corinne
C
Delsol
Georges
G
Touriol
Christian
C
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D015153:Blotting, Western; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D014162:Transfection; D014335:Tropomyosin / Q000235:genetics* / Q000378:metabolism
C498783:TPM3 protein, human; D014335:Tropomyosin; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases