Mutant TP53 interacts with BCAR1 to contribute to cancer cell invasion.

Abstract

BACKGROUND:

Mutant TP53 interacts with other proteins to produce gain-of-function properties that contribute to cancer metastasis. However, the underlying mechanisms are still not fully understood.

METHODS:

Using immunoprecipitation and proximity ligation assays, we evaluated breast cancer anti-estrogen resistance 1 (BCAR1) as a novel binding partner of TP53R273H, a TP53 mutant frequently found in human cancers. The biological functions of their binding were examined by the transwell invasion assay. Clinical outcome of patients was analysed based on TP53 status and BCAR1 expression using public database.

RESULTS:

We discovered a novel interaction between TP53R273H and BCAR1. We found that BCAR1 translocates from the cytoplasm into the nucleus and binds to TP53R273H in a manner dependent on SRC family kinases (SFKs), which are known to enhance metastasis. The expression of full-length TP53R273H, but not the BCAR1 binding-deficient mutant TP53R273HΔ102-207, promoted cancer cell invasion. Furthermore, among the patients with mutant TP53, high BCAR1 expression was associated with a poorer prognosis.

CONCLUSIONS:

The interaction between TP53R273H and BCAR1 plays an important role in enhancing cancer cell invasion. Thus, our study suggests a disruption of the TP53R273H-BCAR1 binding as a potential therapeutic approach for TP53R273H-harbouring cancer patients.

• Authors: Alvin Kunyao Guo, Yoko Itahana, Veerabrahma Pratap Seshachalam, Hui Ying Chow, Sujoy Ghosh, Koji Itahana
• Journal: British journal of cancer (Br J Cancer) Vol. 124 Issue 1 Pg. 299-312 (01 2021) ISSN: 1532-1827 [Electronic] England
• PMID: 33144694 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCAR1 protein, human
• Crk-Associated Substrate Protein
• TP53 protein, human
• Tumor Suppressor Protein p53

Topics

• Cell Line, Tumor
• Crk-Associated Substrate Protein (metabolism)
• Humans
• Mutation
• Neoplasm Invasiveness (genetics)
• Tumor Suppressor Protein p53 (genetics, metabolism)