Proteomics and Biochemical Analyses of Secreted Proteins Revealed a Novel Mechanism by Which ADAM12S Regulates the Migration of Gastric Cancer Cells

Gastric cancer is one of the cancers with the highest
morbidity
and mortality. Although several therapeutic approaches have been developed
to treat this disease, the overall survival rate is still very low
due to metastasis, drug resistance, and so forth. Therefore, it is
necessary to discover new regulatory molecules and signaling pathways
that modulate the metastasis of gastric cancer cells. A Disintegrin
And Metalloprotease 12 (ADAM12) was highly expressed in gastric cancer
tissues and presented in the patient urine. However, it is unclear
whether and how ADAM12 regulates the migration of gastric cancer cells.
In this work, we used the secretome protein enrichment with click
sugars (SPECS) method to purify the secreted glycosylated proteins
and performed quantitative proteomics to identify the secreted proteins
that were differentially regulated by ADAM12S, the short and secreted
form of ADAM12. Our proteomic and biochemical analyses revealed that
ADAM12S upregulated the cell surface glycoprotein CD146, a cell adhesion
molecule and melanoma marker, which was dependent on the catalytic
residue of ADAM12S. Furthermore, we discovered that the ADAM12S-enhanced
migration of gastric cancer cells was, at least partially, mediated
by CD146. This work may help to evaluate whether ADAM12 could be a
potential therapeutic target for the treatment of gastric cancer patients.