The available therapeutic approaches for cervical cancer can seriously
affect the fertility potential of patient; thus, there is a pressing
requirement for less toxic and targeted therapies. The membrane proteome
is a potential source of therapeutic targets; however, despite the
significance of membrane proteins in cancer, proteomic analysis has been
a challenging task due to their unique biochemical properties. The aim
of the present study was to develop an efficient membrane protein
enrichment protocol, and to the best of our knowledge, to compare for
the first time the expression pattern of membrane proteins of one normal
cell line, HCK1T, and three cervical cancer cell lines, C33A, a human
papilloma virus (HPV)-negative cell line, and two HPV-positive cell
lines, SiHa (HPV16(+)) and HeLa (HPV18(+)). The study aimed to identify
the proteins that are involved in cervical carcinogenesis and may
constitute novel drug targets. Membrane protein isolation, liquid
chromatography coupled with tandem mass spectrometry proteomics and
bioinformatics analysis were performed in the membrane fraction of the
informative cervical cell lines following a novel enrichment protocol.
The percentages of membrane and transmembrane proteins in the enrichment
protocol were higher compared with those of the corresponding data
derived from total cell extract analysis. Differentially expressed
proteins were detected by the comparison of the cervical cancer cell
lines with the normal cell line. These proteins constitute molecular
features of cancer pathology and participate in biological pathways
relevant to malignancy, including HIPPO signaling', PI3K/Akt signaling',
cell cycle: G2/M DNA damage checkpoint regulation' and EIF2 signaling'.
These unique membrane protein identifications offer insights on a
previously inaccessible region of the cervical cancer proteome, and may
represent putative diagnostic and prognostic markers, and eventually
therapeutic targets