A proteomics study on human breast cancer cell lines by fluorogenic derivatization-liquid chromatography/tandem mass spectrometry.
Although several molecular markers for human breast cancer exist, their versatility is limited. Here we demonstrate, through a differential proteome analysis utilizing the fluorogenic derivatization-liquid chromatography/tandem mass spectrometry (FD-LC-MS/MS) method between seven cancer cells and one normal cell, that the presence of cooperatively expressed annexin-2 and galectin-1 without tropomyosin-1 in a tissue could be used to diagnose metastatic breast cancer. Interestingly, in a metastatic cancer cell, the expression of the former two together with highly expressed cofilin-1 activates the Rho signal pathway to aggressively form disorganized actin filaments. Despite the excess expression of annexin-2 and galectin-1 in the normal cell, the highly expressed tropomyosin-1 counteracted the activity of cofilin-1 and stabilized the filaments, resulting in the restoration of the disorganization. This phenomenon suggests that enhancement of tropomyosin-1 should be used as therapy for metastatic breast cancer.
Imai
Kazuhiro
K
Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. k-imai@musashino-u.ac.jp
Ichibangase
Tomoko
T
Saitoh
Ryoichi
R
Hoshikawa
Yutaka
Y
D017306:Annexin A2 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods*; D051338:Cofilin 1 / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D037483:Galectin 1 / Q000032:analysis; D006801:Humans; D009362:Neoplasm Metastasis; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014335:Tropomyosin / Q000032:analysis; D015854:Up-Regulation
D017306:Annexin A2; D014408:Biomarkers, Tumor; C495810:CFL1 protein, human; D051338:Cofilin 1; D037483:Galectin 1; C445499:LGALS1 protein, human; D020543:Proteome; C490775:TPM1 protein, human; D014335:Tropomyosin