Metastasis is a process by which cancer cells escape from the location of the primary tumor invading normal tissues at distant organs. Chromosomal instability (CIN) is a hallmark of human cancer, associated with metastasis and therapeutic resistance. The centrosome plays a major role in organizing the microtubule cytoskeleton in animal cells regulating cellular architecture and cell division. Loss of centrosome integrity activates the p38-p53-p21 pathway, which results in cell-cycle arrest or senescence and acts as a cell-cycle checkpoint pathway. Structural and numerical centrosome abnormalities can lead to aneuploidy and CIN. New findings derived from studies on cancer and rare genetic disorders suggest that centrosome dysfunction alters the cellular microenvironment through Rho GTPases, p38, and JNK (c-Jun N-terminal Kinase)-dependent signaling in a way that is favorable for pro-invasive secretory phenotypes and aneuploidy tolerance. We here review recent data on how centrosomes act as complex molecular platforms for Rho GTPases and p38 MAPK (Mitogen activated kinase) signaling at the crossroads of CIN, cytoskeleton remodeling, and immune evasion via both cell-autonomous and non-autonomous mechanisms.

Centrosome dynamics and its role in inflammatory response and metastatic process

Pancione M.;Cerulo L.;
2021

Abstract

Metastasis is a process by which cancer cells escape from the location of the primary tumor invading normal tissues at distant organs. Chromosomal instability (CIN) is a hallmark of human cancer, associated with metastasis and therapeutic resistance. The centrosome plays a major role in organizing the microtubule cytoskeleton in animal cells regulating cellular architecture and cell division. Loss of centrosome integrity activates the p38-p53-p21 pathway, which results in cell-cycle arrest or senescence and acts as a cell-cycle checkpoint pathway. Structural and numerical centrosome abnormalities can lead to aneuploidy and CIN. New findings derived from studies on cancer and rare genetic disorders suggest that centrosome dysfunction alters the cellular microenvironment through Rho GTPases, p38, and JNK (c-Jun N-terminal Kinase)-dependent signaling in a way that is favorable for pro-invasive secretory phenotypes and aneuploidy tolerance. We here review recent data on how centrosomes act as complex molecular platforms for Rho GTPases and p38 MAPK (Mitogen activated kinase) signaling at the crossroads of CIN, cytoskeleton remodeling, and immune evasion via both cell-autonomous and non-autonomous mechanisms.
Centrosome
Chromosome instability
P38 MAPK
Rho GTPases
Tumor microenvironment
Aneuploidy
Animals
Cell Cycle
Cell Cycle Checkpoints
Centrosome
Chromosomal Instability
Cytoskeleton
Humans
Inflammation
JNK Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Microtubules
Neoplasm Metastasis
Neoplasms
Signal Transduction
Tumor Microenvironment
Tumor Suppressor Protein p53
p38 Mitogen-Activated Protein Kinases
rho GTP-Binding Proteins
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.12070/49797
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