Comprehensive fluorogenic derivatization–liquid chromatography/tandem mass spectrometry proteomic analysis of colorectal cancer cell to identify biomarker candidate

Abstract

Existing colorectal cancer biomarkers are insufficient for providing a quick and accurate diagnosis, which is critical for a good prognosis. More appropriate biomarkers are thus needed. To identify new colorectal cancer biomarker candidates, we conducted a comprehensive differential proteomic analysis of six cancer cell lines and a normal cell line, utilizing a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) approach. Two sets of intracellular biomarker candidates were identified: one for colorectal cancer, and the other for metastatic colorectal cancer. Our results suggest that cooperative expression of FABP5 and cyclophilin A might be linked to Her2 signaling. Upregulation of LDHB and downregulation of GAPDH suggest the existence of a specific nonglycolytic energy production pathway in metastatic colorectal cancer cells. Downregulation of 14-3-3ζ/δ, cystatin-B, Ran and thioredoxin could be a result of their secretion, which then stimulates metastasis via activity in the sera and ascitic fluids. We propose a possible flow scheme to describe the dynamics of protein expression in colorectal cancer cells leading to tumor progression and metastasis via cell proliferation, angiogenesis, disorganization of actin filaments and epithelial-mesenchymal transition. Our results suggest that colorectal tumor progression may be regulated by signaling mediated by Her2, hypoxia, and TGFβ.

High expression of Fatty Acid‐Binding Protein 5 promotes cell growth and metastatic potential of colorectal cancer cells

“…Although the expression of FABP5 in CRC cells has been reported 17, the molecular mechanisms underlying the function of FABP5 in CRC cell progression are unknown. Thus, to evaluate the possible roles of FABP5 in CRC cells, we first examined the effect of FABP5 on cell proliferation.…”

“…In addition, other studies reported that FABP5 was upregulated in oral squamous cell carcinoma 10, intrahepatic cholangiocarcinoma 11, pancreatic 12, bladder 13, and triple negative breast cancer 14, 15. Moreover, recent proteomic analyses indicated that FABP5 was also upregulated in hepatocellular carcinoma 16 and CRC cells 17. Thus, as FABP5 is upregulated in several cancer types, it is expected to be a promising prognostic or therapeutic biomarker candidate in these cancers; however, the precise molecular mechanisms underlying FABP5 upregulation and its oncogenic effects in cancer cells remain unclear, despite the extensive efforts of many research groups attempting to clarify the mechanisms.…”

Acetaldehyde and Retinaldehyde-Metabolizing Enzymes in Colon and Pancreatic Cancers

“…Hence, RA induces CARBPII- or FABP5-mediated activation of RAR or PPARβ/δ (respectively), depending on the ratio of FABP5/ CRBPII in the cells [59]. Human colorectal cancer cell lines (specifically, T84, COLO205, SW620, SW480, HCT116 and DLD-1) express ~30-fold higher levels of FABP5 relative to normal colorectal cells (CCD18-Co), suggesting the possibility of pro-proliferative and anti-apoptotic roles for RA in these cells [59, 61]. However, the expression levels of PPARβ/δ in colorectal cancer cells and its role in tumorigenesis are unresolved in various cancers, including CRC [62].…”

Fatty acid binding protein 5 promotes metastatic potential of triple negative breast cancer cells through enhancing epidermal growth factor receptor stability

“…FABP5 has been shown to be involved in a variety of cancers including colon, prostate, and breast cancer [7-9]. Previously, FABP5 mRNA was found to be overexpressed in metastatic breast and prostate cancer cell lines compared to non-metastatic cell lines [9].…”