LAP1 supports nuclear adaptability during constrained melanoma cell migration and invasion

Yaiza Jung-Garcia, Oscar Maiques, Joanne Monger, Irene Rodriguez-Hernandez, Bruce Fanshawe, Marie-Charlotte Domart, Matthew J. Renshaw, Rosa M. Marti, Xavier Matias-Guiu, Lucy M. Collinson, Victoria Sanz-Moreno, Jeremy G. Carlton

Metastasis involves dissemination of cancer cells away from a primary tumour and colonization at distal sites. During this process, the mechanical properties of the nucleus must be tuned since they pose a challenge to the negotiation of physical constraints imposed by the microenvironment and tissue structure. We discovered increased expression of the inner nuclear membrane protein LAP1 in metastatic melanoma cells, at the invasive front of human primary melanoma tumours and in metastases. Human cells express two LAP1 isoforms (LAP1B and LAP1C), which differ in their amino terminus. Here, using in vitro and in vivo models that recapitulate human melanoma progression, we found that expression of the shorter isoform, LAP1C, supports nuclear envelope blebbing, constrained migration and invasion by allowing a weaker coupling between the nuclear envelope and the nuclear lamina. We propose that LAP1 renders the nucleus highly adaptable and contributes to melanoma aggressiveness.