PT  - JOURNAL ARTICLE
AU  - Francesco Roncato
AU  - Ofer Regev
AU  - Sara W. Feigelson
AU  - Sandeep Kumar Yadav
AU  - Lukasz Kaczmarczyk
AU  - Nehora Levi
AU  - Diana Drago-Garcia
AU  - Samuel Ovadia
AU  - Marina Kizner
AU  - Yoseph Addadi
AU  - João Cruz Sabino
AU  - Yossi Ovadya
AU  - Sérgio Fernandes de Almeida
AU  - Ester Feldmesser
AU  - Gabi Gerlitz
AU  - Ronen Alon
TI  - Reduced nuclear lamin A/C enhances cancer cell squeezing through rigid barriers, does not facilitate endothelial crossing, and impairs experimental metastasis
AID  - 10.1101/2020.06.23.167130
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.23.167130
4099  - http://biorxiv.org/content/early/2020/06/24/2020.06.23.167130.short
4100  - http://biorxiv.org/content/early/2020/06/24/2020.06.23.167130.full
AB  - The mechanisms by which the nuclear lamina of tumor cells control their migration and survival are poorly understood. Lamin A and its splice variant lamin C are key nuclear lamina proteins that control nucleus stiffness and chromatin conformation. Genetically reduced lamin A/C levels in two metastatic murine cancer lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, elevated nuclear deformability, reduced H3K9Me3 heterochromatin, and altered gene transcription. Nevertheless, the transendothelial migration capacity of lamin A/C low cells both in vitro and in vivo, through lung capillaries, remained normal. Cancer cell growth within orthotopic implants and DNA damage-induced growth arrest were also insensitive to downregulated lamin A/C expression. Experimental lung metastasis of lamin A/C low cancer cells, however, was markedly reduced. Taken together, our results suggest that reduced lamin A/C expression increases nuclear squeezing through rigid confinements, does not impact intrinsic cancer cell growth and migration, but impairs metastatic survival in lungs.Competing Interest StatementThe authors have declared no competing interest.