Actin-Dependent Mechanism of Tumor Progression Induced by a Dysfunction of P53 Tumor Suppressor

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Mar 28

PMID 38539458

Authors

Natalia Khromova

Maria Vasileva

Vera Dugina

Dmitry Kudlay

Peter Chumakov

Sergei Boichuk

Pavel Kopnin

Affiliations

Soon will be listed here.

Abstract

Cancer cell aggressiveness, marked by actin cytoskeleton reconfiguration critical for metastasis, may result from an imbalanced ratio favoring γ-actin. Dysfunctional p53 emerges as a key regulator of invasiveness and migration in various cancer cells, both in vitro and in vivo. P53 inactivation (via mutants R175H, R248W, R273H, or TP53 repression) significantly enhanced the migration, invasion, and proliferation of human lung adenocarcinoma A549 cells in vitro and in vivo, facilitating intrapulmonary xenograft metastasis in athymic mice. Conversely, wild-type TP53 (TP53 WT) overexpression in p53-deficient non-small- cell lung cancer (NSCLC) H1299 cells substantially reduced proliferation and migration in vitro, effectively curbing orthotopic tumorigenicity and impeding in vivo metastasis. These alterations in cell motility were closely associated with actin cytoskeleton restructuring, favoring γ-actin, and coincided with ERK1/2-mediated signaling activation, unveiling an innovative regulatory mechanism in malignancy progression. Cancer cell aggressiveness, driven by actin cytoskeleton reorganization and a shift towards γ-actin predominance, may be regulated by p53 dysfunction, thereby providing novel insight into tumor progression mechanisms.

Citing Articles

Two-polarized roles of transcription factor FOSB in lung cancer progression and prognosis: dependent on p53 status.

Zhang H, Zhang G, Xiao M, Cui S, Jin C, Yang J J Exp Clin Cancer Res. 2024; 43(1):237.

PMID: 39164746 PMC: 11337850. DOI: 10.1186/s13046-024-03161-1.

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