Patients with right colon cancer showed more mutated BRAF (39.1% vs. 5.4%), mutated PIK3CA (13% vs. 1.4%), poorly differentiated tumor (17.4% vs. 3.4%), and peritoneal involvement (26.1% vs. 8.8%) than those with left colon and rectal cancer.
These results show that almost all the colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.
PI3K pathway mutation is prominent in proximal colon cancers, with PIK3CA exon 20 and PTEN mutations associated with features of the sessile-serrated pathway (MSI-H/CIMP-H/BRAF(mut)), and PIK3CA exon 9 (and to a lesser extent exon 20) mutation associated with features of the traditional serrated pathway (CIMP-L/KRAS(mut)) of tumorigenesis.
In this issue of Cancer Cell, Cheung and colleagues describe two neomorphic PIK3R1 mutants prevalent in endometrial and colon cancer that induce transformation via activation of PI3K-independent pathways.
We verified multiple associations between oncogenic mutations and determined clinicopathological tumor features (1) EGFR A13_deletions are associated with right colon carcinoma (P<0.005), mucinous histotype (P=0.042), G3 grading (P=0.024), and MSI status (P<0.005); (2) PIK3CA mutations are related mucinous histotype (P=0.021); (3) KRAS(G12) and KRAS(G13) mutations are correlated, respectively, with the left and right colon cancer development (P<0.005), and finally (4) MSI is associated with right colon tumors (P<0.005).
Applied to a novel perturbation dataset on PI3K and MAPK pathways in isogenic models of a colon cancer cell line, it generates plausible network hypotheses that explain distinct sensitivities toward various targeted inhibitors due to different PI3K mutants.
Here, we detected its effects on DLD-1 and SW480 (two human colon cancer cell lines) and investigated the dynamic relationship between the 78-kDa glucose-regulatory protein (GRP78) and the phosphoinositide 3-kinase (PI3K)/Akt pathway.
The aim of the present study was to investigate the role of chemokine (C-X-C motif) ligand 8 (CXCL8) in the proliferation, invasiveness and metastasis of colon cancer and its role in the induction of epithelial-mesenchymal transition (EMT) via activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) pathway.
<b>Methods:</b> Patient-derived tumor cells were collected from the ascites of a refractory colon cancer patient with wild-type RAS and PIK3CA mutation.
A preventive potential of high calcium intake against colorectal cancer has been indicated for distal colon cancer, which is inversely associated with high-level CpG island methylator phenotype (CIMP), high-level microsatellite instability (MSI), and BRAF and PIK3CA mutations.