Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis

Francesco Roncato; Ofer Regev; Sara W Feigelson; Sandeep Kumar Yadav; Lukasz Kaczmarczyk; Nehora Levi; Diana Drago-Garcia; Samuel Ovadia; Marina Kizner; Yoseph Addadi; João C Sabino; Yossi Ovadya; Sérgio F de Almeida; Ester Feldmesser; Gabi Gerlitz; Ronen Alon

doi:10.3390/cancers13102383

Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis

Francesco Roncato, Ofer Regev, Sara W Feigelson, Sandeep Kumar Yadav, Lukasz Kaczmarczyk, Nehora Levi, Diana Drago-Garcia, Samuel Ovadia, Marina Kizner, Yoseph Addadi, João C Sabino, Yossi Ovadya, Sérgio F de Almeida, Ester Feldmesser, Gabi Gerlitz, Ronen Alon^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.

Original language	English
Article number	2383
Journal	Cancers
Volume	13
Issue number	10
DOIs	https://doi.org/10.3390/cancers13102383
Publication status	Published - 2 May 2021

Funding

Funding: This research was funded by the Israel Science Foundation (791/17), the Minerva Stiftung, GIF (I-1470-412.13/2018), the EU Horizon 2020 Research and Innovation Program (RiboMed 857119), as well as grants from the Moross Integrated Cancer Center, the Yeda-Sela Center for Basic Research, the Helen and Martin Kimmel Institute for Stem Cell Research, the Meyer Henri Cancer Endowment, and from William and Marika Glied and Carol A. Milett. G.G.’s research is funded by the Israel Cancer Association (20201181).

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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Roncato, F., Regev, O., Feigelson, S. W., Yadav, S. K., Kaczmarczyk, L., Levi, N., Drago-Garcia, D., Ovadia, S., Kizner, M., Addadi, Y., Sabino, J. C., Ovadya, Y., de Almeida, S. F., Feldmesser, E., Gerlitz, G., & Alon, R. (2021). Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis. Cancers, 13(10), Article 2383. https://doi.org/10.3390/cancers13102383

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title = "Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis",

abstract = "The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.",

author = "Francesco Roncato and Ofer Regev and Feigelson, {Sara W} and Yadav, {Sandeep Kumar} and Lukasz Kaczmarczyk and Nehora Levi and Diana Drago-Garcia and Samuel Ovadia and Marina Kizner and Yoseph Addadi and Sabino, {Jo{\~a}o C} and Yossi Ovadya and {de Almeida}, {S{\'e}rgio F} and Ester Feldmesser and Gabi Gerlitz and Ronen Alon",

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Roncato, F, Regev, O, Feigelson, SW, Yadav, SK, Kaczmarczyk, L, Levi, N, Drago-Garcia, D, Ovadia, S, Kizner, M , Addadi, Y, Sabino, JC, Ovadya, Y, de Almeida, SF, Feldmesser, E, Gerlitz, G & Alon, R 2021, 'Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis', Cancers, vol. 13, no. 10, 2383. https://doi.org/10.3390/cancers13102383

TY - JOUR

T1 - Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis

AU - Roncato, Francesco

AU - Regev, Ofer

AU - Feigelson, Sara W

AU - Yadav, Sandeep Kumar

AU - Kaczmarczyk, Lukasz

AU - Levi, Nehora

AU - Drago-Garcia, Diana

AU - Ovadia, Samuel

AU - Kizner, Marina

AU - Addadi, Yoseph

AU - Sabino, João C

AU - Ovadya, Yossi

AU - de Almeida, Sérgio F

AU - Feldmesser, Ester

AU - Gerlitz, Gabi

AU - Alon, Ronen

PY - 2021/5/2

Y1 - 2021/5/2

N2 - The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.

AB - The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.

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DO - 10.3390/cancers13102383

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JF - Cancers

IS - 10

M1 - 2383

ER -

Reduced lamin a/c does not facilitate cancer cell transendothelial migration but compromises lung metastasis

Abstract

Funding

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