Lamin A/C as a Molecular Link Between Nuclear Organization, Chromatin Dynamics, and Tumor Progression

TL;DR

Lamin A/C connects nuclear structure and function, influencing cancer progression in complex, context-dependent ways.

Contribution

Lamin A/C is redefined as a dynamic regulator linking nuclear mechanics, chromatin dynamics, and tumor progression.

Findings

Lamin A/C regulates chromatin organization and transcription by linking nuclear mechanics and epigenetics.

Its role in cancer is context-dependent, leading to varied prognostic associations across tumor types.

Lamin A/C functions as a nuclear rheostat, balancing cell deformability and genome stability in tumor progression.

Abstract

What are the main findings?
Lamin A/C is a dynamic mechano-epigenetic regulator that links nuclear mechanics with chromatin organization and transcription.In cancer, lamin A/C functions in a strongly context-dependent manner, yielding heterogeneous and sometimes opposing prognostic associations across tumor types.

Lamin A/C is a dynamic mechano-epigenetic regulator that links nuclear mechanics with chromatin organization and transcription.

In cancer, lamin A/C functions in a strongly context-dependent manner, yielding heterogeneous and sometimes opposing prognostic associations across tumor types.

What are the implications of the main findings?
Lamin A/C might be viewed as a nuclear rheostat that regulates tumor cell behavior along a spectrum from deformability and plasticity to mechanical robustness and genome stability.Clinical translation requires context-dependent strategies that use lamin A/C features for patient stratification and target its associated pathways for treatment while preserving normal tissue function.

Lamin A/C might be viewed as a nuclear rheostat that regulates tumor cell behavior along a spectrum from deformability and plasticity to mechanical robustness and genome stability.

Clinical translation requires context-dependent strategies that use lamin A/C features for patient stratification and target its associated pathways for treatment while preserving normal tissue function.

Lamin A/C is emerging as a promising candidate regulator at the intersection of nuclear mechanics, chromatin organization, and gene regulation, linking structure and regulation, mechanics and epigenetics, constraint and plasticity. Lamin A/C was previously considered a static structural scaffold; however, it is now recognized as a dynamic component of nuclear organization that links physical cues to epigenetic and transcriptional states. Lamin A/C regulates three-dimensional genome structure, constrains chromatin mobility, and influences cell transitions between plastic and committed states through its interactions with heterochromatin at the nuclear periphery and active chromatin domains in the nuclear interior. In cancer, these functions appear to be dependent on the context. Lamin A/C has been implicated in crucial biological processes, including invasion, survival under mechanical stress, lineage plasticity, and therapeutic response. Its prognostic value varies across tumor types. This heterogeneity indicates that lamin A/C does not function as a traditional oncogene or oncosuppressor; instead, it operates as a nuclear rheostat, influencing the behavior and development of tumor cells. This review examines the potential clinical benefits of lamin A/C while considering its implications for normal tissue functions. It aims to improve understanding of cellular adaptability and vulnerability in cancer through the exploration of lamin A/C biology.

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