细胞生物学-自然2013-09-05 2:58 AM

The collagen receptor discoidin domain receptor 2 stabilizes SNAIL1 to facilitate breast cancer metastasis : Nature Cell Biology : Nature Publishing Group

Increased stromal collagen deposition in human breast tumours correlates with metastases. We show that activation of the collagen I receptor DDR2 (discoidin domain receptor 2) regulates SNAIL1 stability by stimulating ERK2 activity, in a Src-dependent manner. Activated ERK2 directly phosphorylates SNAIL1, leading to SNAIL1 nuclear accumulation, reduced ubiquitylation and increased protein half-life. DDR2-mediated stabilization of SNAIL1 promotes breast cancer cell invasion and migration in vitro, and metastasis in vivo. DDR2 expression was observed in most human invasive ductal breast carcinomas studied, and was associated with nuclear SNAIL1 and absence of E-cadherin expression. We propose that DDR2 maintains SNAIL1 level and activity in tumour cells that have undergone epithelial–mesenchymal transition (EMT), thereby facilitating continued tumour cell invasion through collagen-I-rich extracellular matrices by sustaining the EMT phenotype. As such, DDR2 could be an RTK (receptor tyrosine kinase) target for the treatment of breast cancer metastasis.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

细胞生物学-自然

0 Following 0 Fans 0 Projects 20 Articles

SIMILAR ARTICLES

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated th

Read More

The transition zone is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules are heav

Read More

The adult mouse subependymal zone (SEZ) harbours adult neural stem cells (aNSCs) that give rise to neuronal and oligodendroglial progeny. However it is

Read More

Oligodendrocytes—the myelin-forming cells of the central nervous system—can be regenerated during adulthood. In adults, new oligodendrocytes originate

Read More

How different integrins that bind to the same type of extracellular matrix protein mediate specific functions is unclear. We report the functional anal

Read More

To learn more about cancer-associated fibroblasts (CAFs), we have isolated fibroblasts from different stages of breast cancer progression and analysed

Read More

The lysosomal–autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the t

Read More

Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereb

Read More

Fat is stored or mobilized according to food availability. Malfunction of the mechanisms that ensure this coordination underlie metabolic diseases in h

Read More

Increased stromal collagen deposition in human breast tumours correlates with metastases. We show that activation of the collagen I receptor DDR2 (disc

Read More