Proteomic profiling of murine melanoma treated with bone morphogenetic protein (BMP) signaling inhibitor

ABSTRACT: Melanoma is a highly aggressive skin cancer, which has the fastest and second fastest growing incidence of any cancer in men and women, respectively. Although melanoma accounts for 5% of skin cancers, it is responsible for 80% of deaths related to skin cancers. The lifetime risk of melanoma is currently estimated to be 1 in 75 and is rising every year. The present study shows that inhibition of bone morphogenetic protein (BMP) signaling pathway is a potential target for treating metastatic melanoma. To characterize the underlying signaling mechanism, comparative proteomic profile of the mouse melanoma tissue treated with and BMP inhibitor (LDN193189) with untreated controls was performed using liquid chromatography-tandem mass spectrometry. Our mass spectrometry data analysis leads to identification of a total of 3231 nonredundant proteins. Of the 3231 proteins, 117 were up-regulated (fold change≥ 1.5) while 14 were down-regulated (fold change ≤ 0.66). Pathway enrichment analysis showed that altered proteins were primarily grouped into: regulation of actin cytoskeleton, phagosomes, proteoglycans in cancer, Focal adhesion, ECM receptor interaction and fatty acid metabolism pathway. Our studies suggest that inhibition of the BMP signaling cascade with small molecule inhibitors decreased the expression of the MT1 and MT2 (metallothionine 1 and 2) which are well known for the antiapoptotic, antioxidant, proliferative, and angiogenic effects in cancer.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skin

DISEASE(S): Melanoma

SUBMITTER: Keshava Prasad T. S.  

LAB HEAD: T. S. Keshava Prasad

PROVIDER: PXD016088 | Pride | 2022-02-15

REPOSITORIES: Pride