3 research outputs found
Proteomic Analysis of Colorectal Cancer Metastasis: Stathmin-1 Revealed as a Player in Cancer Cell Migration and Prognostic Marker
Metastasis accounts largely for the high mortality rate
of colorectal
cancer (CRC) patients. In this study, we performed comparative proteome
analysis of primary CRC cell lines HCT-116 and its metastatic derivative
E1 using 2-D DIGE. We identified 74 differentially expressed proteins,
many of which function in transcription, translation, angiogenesis
signal transduction, or cytoskeletal remodeling pathways, which are
indispensable cellular processes involved in the metastatic cascade.
Among these proteins, stathmin-1 (STMN1) was found to be highly up-regulated
in E1 as compared to HCT-116 and was thus selected for further functional
studies. Our results showed that perturbations in STMN1 levels resulted
in significant changes in cell migration, invasion, adhesion, and
colony formation. We further showed that the differential expression
of STMN1 correlated with the cells’ metastatic potential in
other paradigms of CRC models. Using immunohistochemistry, we also
showed that STMN1 was highly expressed in colorectal primary tumors
and metastatic tissues as compared to the adjacent normal colorectal
tissues. Furthermore, we also showed via tissue microarray analyses
of 324 CRC tissues and Kaplan–Meier survival plot that CRC
patients with higher expression of STMN1 have poorer prognosis
Proteomic Analysis of Colorectal Cancer Metastasis: Stathmin-1 Revealed as a Player in Cancer Cell Migration and Prognostic Marker
Metastasis accounts largely for the high mortality rate
of colorectal
cancer (CRC) patients. In this study, we performed comparative proteome
analysis of primary CRC cell lines HCT-116 and its metastatic derivative
E1 using 2-D DIGE. We identified 74 differentially expressed proteins,
many of which function in transcription, translation, angiogenesis
signal transduction, or cytoskeletal remodeling pathways, which are
indispensable cellular processes involved in the metastatic cascade.
Among these proteins, stathmin-1 (STMN1) was found to be highly up-regulated
in E1 as compared to HCT-116 and was thus selected for further functional
studies. Our results showed that perturbations in STMN1 levels resulted
in significant changes in cell migration, invasion, adhesion, and
colony formation. We further showed that the differential expression
of STMN1 correlated with the cells’ metastatic potential in
other paradigms of CRC models. Using immunohistochemistry, we also
showed that STMN1 was highly expressed in colorectal primary tumors
and metastatic tissues as compared to the adjacent normal colorectal
tissues. Furthermore, we also showed via tissue microarray analyses
of 324 CRC tissues and Kaplan–Meier survival plot that CRC
patients with higher expression of STMN1 have poorer prognosis
Identification of Potential Pathways Involved in Induction of Apoptosis by Butyrate and 4‑Benzoylbutyrate in HT29 Colorectal Cancer Cells
Butyrate and its analogues have long been investigated as potential
chemotherapeutic agents. Our previous structure–activity relationship
studies of butyrate analogues revealed that 4-benzoylbutyrate had
comparable in vitro effects to butyrate when used to treat HT29 and
HCT116 colorectal cancer cell lines. The aim of this study was to
identify potential mechanisms associated with the antitumorigenic
effects of 4-benzoylbutyrate. In this study, butyrate, 3-hydroxybutyrate
and 4-benzoylbutyrate were also investigated for their effects on
histone deacetylase (HDAC) activity and histone H4 acetylation in
HT29 and HCT116 cells. The biological effects of these analogues on
HT29 cells were further investigated using quantitative proteomics
to determine the proteins potentially involved in their apoptotic
and antiproliferative effects. Because 3-hydroxybutyrate had minimal
to no effect on apoptosis, proliferation or HDAC activity, this analogue
was used to identify differentially expressed proteins that were potentially
specific to the apoptotic effects of butyrate and/or 4-benzoylbutyrate.
Butyrate treatment inhibited HDAC activity and induced H4 acetylation.
4-Benzoylbutyrate inhibited HDAC activity but failed to enhance H4
acetylation. Proteomic analysis revealed 20 proteins whose levels
were similarly altered by both butyrate and 4-benzoylbutyrate. Proteins
that showed common patterns of differential regulation in the presence
of either butyrate or 4-benzoylbutyrate included c-Myc transcriptional
targets, proteins involved in ER homeostasis, signal transduction
pathways and cell energy metabolism. Although an additional 23 proteins
were altered by 4-benzoylbutyrate uniquely, further work is required
to understand the mechanisms involved in its apoptotic effects