A MAP1B-cortactin-Tks5 axis regulates TNBC invasion and tumorigenesis.
J Cell Biol
; 223(3)2024 03 04.
Article
in En
| MEDLINE
| ID: mdl-38353696
ABSTRACT
The microtubule-associated protein MAP1B has been implicated in axonal growth and brain development. We found that MAP1B is highly expressed in the most aggressive and deadliest breast cancer subtype, triple-negative breast cancer (TNBC), but not in other subtypes. Expression of MAP1B was found to be highly correlated with poor prognosis. Depletion of MAP1B in TNBC cells impairs cell migration and invasion concomitant with a defect in tumorigenesis. We found that MAP1B interacts with key components for invadopodia formation, cortactin, and Tks5, the latter of which is a PtdIns(3,4)P2-binding and scaffold protein that localizes to invadopodia. We also found that Tks5 associates with microtubules and supports the association between MAP1B and α-tubulin. In accordance with their interaction, depletion of MAP1B leads to Tks5 destabilization, leading to its degradation via the autophagic pathway. Collectively, these findings suggest that MAP1B is a convergence point of the cytoskeleton to promote malignancy in TNBC and thereby a potential diagnostic and therapeutic target for TNBC.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adaptor Proteins, Vesicular Transport
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Cortactin
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Triple Negative Breast Neoplasms
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Microtubule-Associated Proteins
Type of study:
Prognostic_studies
Limits:
Animals
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Female
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Humans
Language:
En
Journal:
J Cell Biol
Year:
2024
Document type:
Article
Affiliation country: