GPC1 promotes the growth and migration of colorectal cancer cells through regulating the TGF-β1/SMAD2 signaling pathway

Abstract

In this study, we analyzed GPC family genes in colorectal cancer (CRC) and the possible mechanism of action of GPC1 in CRC. CRC patient data were extracted from The Cancer Genome Atlas, and the prognostic significance of GPC1 expression and its association with clinicopathological features were identified by Kolmogorov–Smirnov test. CRC patients with high GPC1 expression had poor overall survival compared with patients with low GPC1 expression. In vitro experiments demonstrated that knockdown of GPC1 significantly inhibited the proliferation and migration and promoted cell apoptosis in CRC cell lines. Gene Ontology analysis of differential genes indicated that GPC1 may influence the TGF-β1 signaling pathway. Additional experiments revealed that silencing GPC1 suppressed the levels of TGF-β1 and p-SMAD2 but increased the expression of SMAD2. Taken together, these findings suggest that GPC1 may function as a tumor promoter in CRC cells through promoting TGF-β signaling pathway. Our results also indicate that GPC1 may serve as a critical effector in CRC progression and a new potential target for CRC therapy.

Multifactor dimensionality reduction method identifies novel SNP interactions in the WNT protein interaction networks that are associated with recurrence risk in colorectal cancer

“…A significant portion of the genes was already linked to colorectal cancer pathogenesis or progression/prognosis by previous studies. For example, expression levels, deletion, or biological functions of ROR2, SFRP1, LRP6, PITX2, WLS, GPC1, HCK, HPN, MKRN2, and DDX58 were associated with disease features, patient outcomes/prognosis, or invasive and other malignant features of colorectal tumors (46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57). This literature information supports our findings and can be partly attributed to the fact that the Wnt pathway is one of the most studied pathways in colorectal cancer, increasing the chances of finding literature information on genes functioning in Wnt-related biological processes.…”

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis

“…Similar to CA19-9, GPC1 upregulation has also been observed in other cancer types. [17][18][19][20][21][22][23] Therefore, we measured the expression of GPC1 Exo-mRNA and tMV-mProtein in serum samples from late-stage breast cancer (BC) patients (MSKCC, n = 31), plasma samples from late-stage hepatocellular carcinoma (HCC) patients (National Health Research Institute (NHRI) Biobank, n = 11), and plasma samples from late-stage esophageal cancer (EC) patients (Chang Guan Memorial Hospital (CGMH), n = 11). We used plasma samples from Stage I PDAC patients from TVGH (n = 30) as a basis for comparison.…”

“…[ 16 ] Glypican‐1 (GPC1) expression is notably elevated in various cancer types, including PDAC, [ 15 ] breast cancer, [ 17 ] esophageal squamous cell carcinoma, [ 18 ] glioblastoma, [ 19 ] colorectal cancer, [ 20 ] hepatocellular carcinoma, [ 21 ] and cervical cancer. [ 22 ] Transfecting GPC1 RNAi has demonstrated the ability to impede the mitogenic response in cultured colorectal cancer cells, [ 23 ] establishing GPC1 as a potential biomarker for cancer detection.…”