LIM and SH3 Protein Dynamics in Cancer Progression

The LIM and Src homology 3 (SH3) domain-containing proteins constitute a versatile family of structural and signalling molecules that orchestrate cytoskeletal architecture, cell motility and transcriptional regulation in cancer. Core members such as LIM and SH3 protein 1 (LASP1) and its paralogue LASP2 engage in focal adhesion assembly, invadopodia formation and dynamic actin remodelling, facilitating tumour cell proliferation and invasion. Through direct interactions with oncogenic receptors, kinases and scaffolding proteins, these dual-domain adaptors integrate extracellular cues into intracellular pathways, notably the PI3K/AKT, FAK and MAPK cascades. Aberrant expression or subcellular mislocalisation of LIM-SH3 proteins correlates with advanced stage, metastatic spread and poor prognosis across multiple tumour types. Beyond structural roles, emerging data reveal nuclear functions of LIM-SH3 proteins in gene regulation, MMP secretion and chemoresistance. Their central position in signal transduction and the extracellular matrix landscape underscores both their value as prognostic biomarkers and as candidate targets for therapeutic interference. Continued elucidation of the dynamic interplay between LIM and SH3 modules and their binding partners promises new insights into metastasis and may inform the development of domain-specific inhibitors.

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LIM and SH3 Protein Dynamics in Cancer Progression publication trend

The graph below shows the total number of articles in lim and sh3 protein dynamics in cancer progression across all publications each year (not limited to Nature Index journals).

Technical terms

LIM domain: A zinc-finger motif that mediates protein–protein interactions and assembly of multi-protein complexes.

SH3 domain: A small modular domain that binds proline-rich sequences, facilitating signal transduction and cytoskeletal linkage.

Focal adhesions: Multi-molecular assemblies that anchor the actin cytoskeleton to the extracellular matrix and transduce mechanical signals.

Invadopodia: Actin-rich protrusions that concentrate matrix-degrading enzymes to facilitate extracellular matrix invasion.

PI3K/AKT pathway: A kinase cascade central to cell survival, growth and metabolism, often deregulated in cancer.

Epithelial-mesenchymal transition (EMT): A phenotypic switch by which epithelial cells acquire migratory and invasive mesenchymal traits.

References

1. The LIM and SH3 domain protein family: structural proteins or signal transducers or both?. Molecular Cancer (2008).
2. New Frontiers for the Cytoskeletal Protein LASP1. Frontiers in Oncology (2018).
3. LIM and SH3 protein 1 regulates cell growth and chemosensitivity of human glioblastoma via the PI3K/AKT pathway. BMC Cancer (2018).
4. An update on the LIM and SH3 domain protein 1 (LASP1): a versatile structural, signaling, and biomarker protein. Oncotarget (2014).
5. LASP1 promotes proliferation, metastasis, invasion in head and neck squamous cell carcinoma and through direct interaction with HSPA1A. Journal of Cellular and Molecular Medicine (2019).