Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.10.2 (
focal adhesion kinase
)
44,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Annexin A4 (encoded by the
ANXA4
gene) is a calcium ion (Ca
2+
)- and phospholipid-binding protein of the Annexin family. In this study, we checked the expression profile of
ANXA4
in basal-like breast cancer (BLBC) and its association with survival outcomes using pan-cancer data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Then, using MDA-MB-231 and MDA-MB-468 cells, we explored the functional role of ANXA4 in regulating a cancer-related signaling pathway and identified potential partners of ANXA4. The results showed that expression of total
ANXA4
and the two dominant
ANXA4 protein
-coding transcripts (ENST00000409920.5 and ENST00000394295.4) was consistently upregulated in tumor tissues compared with normal breast tissues. BLBC patients with high
ANXA4
expression had significantly worse overall survival, progression-free survival, and disease-free survival than those with low
ANXA4
expression. ANXA4 could positively modulate cyclin D1 expression and G1/S progression in the two cell lines. An
in vivo
tumor model showed that
ANXA4
inhibition significantly slowed the growth of tumors derived from the two BLBC cell lines. ANXA4 could increase
JAK1
expression and STAT3 phosphorylation (Y705). ANXA4 colocalized with ANXA1 in some MDA-MB-231 cells. A co-immunoprecipitation assay confirmed direct binding between ANXA4 and ANXA1. Knockdown of
ANXA1
reduced
JAK1
expression and STAT3 phosphorylation and impaired ANXA4-induced upregulation of
JAK1
and p-STAT3. In conclusion, this study revealed that aberrant
ANXA4
upregulation is associated with poor survival in BLBC. ANXA4 could activate JAK-STAT3 signaling by elevating the expression of
JAK1
and p-STAT3, which was mediated by direct interaction with ANXA1.
...
PMID:ANXA4 Activates JAK-STAT3 Signaling by Interacting with ANXA1 in Basal-Like Breast Cancer. 3255 56
