Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Nov 21;15(23):5501.
doi: 10.3390/cancers15235501.

The Multifaceted Roles of Lamins in Lung Cancer and DNA Damage Response

Janina Janetzko  1 , Sebastian Oeck  1 , Alexander Schramm  1
Affiliations
Review

The Multifaceted Roles of Lamins in Lung Cancer and DNA Damage Response

Janina Janetzko et al. Cancers (Basel). .

Abstract

Emerging evidence suggests that lamin functions are not limited to maintaining the structural integrity of the nucleus in eukaryotic cells but that these functions affect many facets of cancer biology. An increasing number of reports suggest that adaptive changes in the lamin subtype composition within the nuclear lamina could affect essential features of cancer development and aggressiveness. These include regulation of cellular stiffness and mobility as well as epithelial-to-mesenchymal transition (EMT), all of which directly impact the metastatic properties of cancer cells. Additionally, insights from studies on the physiological functions of lamins suggest that cancer cells could hijack the ability of lamins to modify chromatin accessibility, cell cycle regulation, and DNA damage response. Here, we present a comprehensive overview of the role of lamins in lung cancer and DNA damage response, which is commonly evoked by lung cancer therapies. Collectively, this information should help better understand the sometimes-conflicting reports on lamin functions in lung cancer as well as in other cancer types.

Keywords: DNA repair; kinases; lamin composition; lamins; lung cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Lamin family members and prominent phosphorylation sites. (A) Schematic summary of the structure common to all lamin subtypes. (B) Overview of known lamin splice variants encoded by LMNA (blue), LMNB1 (brown), and LMNB2 (orange). (C) Major lamin phosphorylation sites targeted by oncogenes including CDK1 and AKT (PKB).
Figure 2
Figure 2
The multifaceted roles of lamins (orange, green) in maintaining cellular integrity and the DNA damage response in physiological conditions (left) and altered functions in lung cancer (right). Major regulators of cell cycle (Cyclins D and E, p53, 53BP1), proliferation (AKT), and chromatin accessibility (EZH2) interact with the lamin network to maintain cellular homeostasis and to coordinate structural integrity before and during cell division. In cancer, hijacking of these functions either by the mutational activation or the inactivation of proto-oncogenes and tumor suppressor genes contributes to the modulation and reprogramming of the lamin network, respectively. Specifically, aberrant AKT and cyclin D signaling in lung cancer induces B-type lamin depolymerization and enhanced proliferation, while the EZH2-mediated regulation of lamin A/C alters the transcriptional control of factors promoting cancer aggressiveness and EMT by down-regulating E-cadherin and upregulating vimentin. The arrows show up- and downregulation of the indicated factors altered by changes in lamin levels.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Lammerding J., Fong L.G., Ji J.Y., Reue K., Stewart C.L., Young S.G., Lee R.T. Lamins A and C but not lamin B1 regulate nuclear mechanics. J. Biol. Chem. 2006;281:25768–25780. doi: 10.1074/jbc.M513511200. - DOI - PubMed
    1. Fisher D.Z., Chaudhary N., Blobel G. cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Proc. Natl. Acad. Sci. USA. 1986;83:6450–6454. doi: 10.1073/pnas.83.17.6450. - DOI - PMC - PubMed
    1. Machiels B.M., Zorenc A.H., Endert J.M., Kuijpers H.J., van Eys G.J., Ramaekers F.C., Broers J.L. An alternative splicing product of the lamin A/C gene lacks exon 10. J. Biol. Chem. 1996;271:9249–9253. doi: 10.1074/jbc.271.16.9249. - DOI - PubMed
    1. Bouvier D., Hubert J., Seve A.P., Bouteille M. Characterization of lamina-bound chromatin in the nuclear shell isolated from HeLa cells. Exp. Cell Res. 1985;156:500–512. doi: 10.1016/0014-4827(85)90557-9. - DOI - PubMed
    1. Sullivan T., Escalante-Alcalde D., Bhatt H., Anver M., Bhat N., Nagashima K., Stewart C.L., Burke B. Loss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy. J. Cell Biol. 1999;147:913–920. doi: 10.1083/jcb.147.5.913. - DOI - PMC - PubMed

LinkOut - more resources