Phosphoproteome of a patient-matched cell line model of colon cancer metastasis

ABSTRACT: The contributions of phosphorylation-mediated signaling networks to colon cancer metastasis are poorly defined. To better understand the role of constitutive signaling alterations in cancer progression, the global phosphoproteomes of the SW480 and SW620 cell lines were compared by LC-MS/MS. These patient-matched cell lines were derived from a primary colon tumor and a lymph node metastasis, respectively. Network analysis of the significantly altered phosphosites revealed differential regulation in cellular adhesion, mitosis, and mRNA translational machinery. Among the latter group were sites on phosphoproteins with known roles in mRNA biogenesis and splicing, transport through the nuclear pores, initiating translation, as well as mRNA stability and degradation. Though alterations in these processes have been associated with oncogenic transformation, control of mRNA stability has typically not been associated with cancer progression. Notably, the single phosphosite with the greatest relative change in SW620 was Ser2 on eIF2S2, suggesting that SW620 cells translate faster or with greater efficiency than SW480 cells. These broad changes in the regulation of translation also occur without over-expression of eIF4E. Altogether, this work shows that metastatic cells exhibit constitutive changes to the phosphoproteome, and that mRNA stability and translational efficiency may be important targets of deregulation during cancer progression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Alissa Schunter  

LAB HEAD: Amanda B. Hummon

PROVIDER: PXD003708 | Pride | 2017-01-06

REPOSITORIES: Pride