TY - JOUR
T1 - Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma
AU - Navarro Barea, Natalia
AU - Molist, Carla
AU - Sansa-Girona, Júlia
AU - Zarzosa, Patricia
AU - Gallo-Oller, Gabriel
AU - Pons, Guillem
AU - Magdaleno, Ainara
AU - Guillén, Gabriela
AU - Hladun, Raquel
AU - Garrido, Marta
AU - Segura, Miguel F
AU - Hontecillas-Prieto, L.
AU - de Álava, E.
AU - Ponsati, B.
AU - Fernández-Carneado, J.
AU - Almazán-Moga, Anna
AU - Vallès-Miret, M.
AU - Farrera-Sinfreu, J.
AU - Sánchez de Toledo Codin, Josep
AU - Moreno, Lucas
AU - Roma, Josep
PY - 2022
Y1 - 2022
N2 - The majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model.
AB - The majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model.
KW - Cancer
KW - Dissemination
KW - Paediatric cancer
KW - Progression
KW - Solid tumours
U2 - 10.1007/s00018-022-04557-y
DO - 10.1007/s00018-022-04557-y
M3 - Article
C2 - 36221013
SN - 1420-9071
VL - 79
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 11
ER -
