Why is the colorectal cancer signaling pathway bypassed?

"This study analyzed the expression of PDGFR and VEGFR in primary colon cancer tissues and CRC cell lines in order to better determine their expression profiles
.
In addition, we analyzed the cross-binding
of putative PDGF to VEGFR and EGFR in HT29 cells lacking PDGFR expression.
”

On October 19, 2022, a new research paper was published in Volume 13 of Oncotarget, titled "Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer"

In addition to growth factor-mediated signaling pathways such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), platelet-derived growth factor (PDGF) signaling pathways appear to play a crucial role
in tumor development and development.

Recently, researchers provided evidence of upregulation of PDGF expression in UICC stage I-IV primary colorectal cancer (CRC) and demonstrated the induction
of the PI3K/Akt/mTOR signaling pathway in PDGF-mediated CRC cell lines.
In this study, the researchers sought to follow up on their previous findings and explore the potential
for cross-binding of alternative receptors for PDGF in CRCs.

"Our analysis of primary human colon tumor samples showed upregulation
of PDGFRβ, VEGFR1, and VEGFR2 genes in UICC stage I-III tumors.
"

Immunohistological analysis revealed co-expression of PDGF and its putative cross-binding
partners VEGFR2 and EGFR.
The team then analyzed PDGFRα, PDGFRβ, VEGFR1, and VEGFR2 protein expression
in several CRC cell lines.
They found that these receptors were expressed differently
in the cell lines studied.

Interestingly, Caco-2 and SW480 cells expressed all the analyzed receptors, while HT29 cells expressed only VEGFR1 and VEGFR2
.
However, in the absence of PDGFR expression, PDGF stimulation of HT29 cells led to upregulation of VEGFR1 and VEGFR2 expression and mimicked the effect of
VEGF stimulation.
In addition, in the case of simultaneous treatment with VEGFR or EGFR inhibitors, PDGF restored the proliferation
of HT29 cells.

"Our findings provide some preliminary evidence for cross-signaling of PDGF in colorectal cancer through alternative receptors and support anti-PDGF therapy as a combination strategy with VEGF and EGF targeting, even in
tumors lacking PDGFR expression.
"