4 research outputs found
Proteomic Characterization of Transcription and Splicing Factors Associated with a Metastatic Phenotype in Colorectal Cancer
We investigated new transcription
and splicing factors associated
with the metastatic phenotype in colorectal cancer. A concatenated
tandem array of consensus transcription factor (TF)-response elements
was used to pull down nuclear extracts in two different pairs of colorectal
cancer cells, KM12SM/KM12C and SW620/480, genetically related but
differing in metastatic ability. Proteins were analyzed by label-free
LC–MS and quantified with MaxLFQ. We found 240 proteins showing
a significant dysregulation in highly metastatic KM12SM cells relative
to nonmetastatic KM12C cells and 257 proteins in metastatic SW620
versus SW480. In both cell lines there were similar alterations in
genuine TFs and components of the splicing machinery like UPF1, TCF7L2/TCF-4,
YBX1, or SRSF3. However, a significant number of alterations were
cell-line specific. Functional silencing of MAFG, TFE3, TCF7L2/TCF-4,
and SRSF3 in KM12 cells caused alterations in adhesion, survival,
proliferation, migration, and liver homing, supporting their role
in metastasis. Finally, we investigated the prognostic value of the
altered TFs and splicing factors in cancer patients. SRSF3 and SFPQ
showed significant prognostic value. We observed that SRSF3 displayed
a gradual loss of expression associated with cancer progression. Loss
of SRSF3 expression was significantly associated with poor survival
and shorter disease-free survival, particularly in early stages, in
colorectal cancer
Proteomic Characterization of Transcription and Splicing Factors Associated with a Metastatic Phenotype in Colorectal Cancer
We investigated new transcription
and splicing factors associated
with the metastatic phenotype in colorectal cancer. A concatenated
tandem array of consensus transcription factor (TF)-response elements
was used to pull down nuclear extracts in two different pairs of colorectal
cancer cells, KM12SM/KM12C and SW620/480, genetically related but
differing in metastatic ability. Proteins were analyzed by label-free
LC–MS and quantified with MaxLFQ. We found 240 proteins showing
a significant dysregulation in highly metastatic KM12SM cells relative
to nonmetastatic KM12C cells and 257 proteins in metastatic SW620
versus SW480. In both cell lines there were similar alterations in
genuine TFs and components of the splicing machinery like UPF1, TCF7L2/TCF-4,
YBX1, or SRSF3. However, a significant number of alterations were
cell-line specific. Functional silencing of MAFG, TFE3, TCF7L2/TCF-4,
and SRSF3 in KM12 cells caused alterations in adhesion, survival,
proliferation, migration, and liver homing, supporting their role
in metastasis. Finally, we investigated the prognostic value of the
altered TFs and splicing factors in cancer patients. SRSF3 and SFPQ
showed significant prognostic value. We observed that SRSF3 displayed
a gradual loss of expression associated with cancer progression. Loss
of SRSF3 expression was significantly associated with poor survival
and shorter disease-free survival, particularly in early stages, in
colorectal cancer