Table 1 NTS, NTSR, downstream signaling pathways and main molecular mechanisms related to primary tumors, EMT and tumor microenvironement, and involved in each of the four digestive cancers described (GC, PDAC, HCC, and CRC).
From: Neurotensin pathway in digestive cancers and clinical applications: an overview
NTS and receptors | Activated signaling pathways, downstream stimulated effectors and upregulated genes | Tumor microenvironment modulation (NTS/IL-8) | |
|---|---|---|---|
GC | NTS (secreted), NTSR1 | - PKC - ERK1/2 - PI3K/AKT | Not described |
PDAC | 1- NTS, NTSR1 2- NTS/sortilin | - PKC-dependent ERK1/2 - PI3K/AKT RhoGTPases | Not described |
HCC | NTS, NTSR1 | Wnt/β-catenin → NTSR1, EGFR | Stem cells maintenance RAF-1, ERK1/2 → IL-8, CXCL1 EMT, cancer, and stromal cell infiltration within tumors MAPK, NFκB → IL-8 |
CRC | 1- NTS, NTSR1 2- sortilin/sSortilin (secreted) | - PKB, β-catenin → Cyclin D1 - Ca2+ release - RhoGTPases, NFκB → IL-8 - AKT by EGFR-transactivation dependent (HT29, HCT116) - MAPK-ERK1/2 by EGFR-transactivation dependent (HT29) or PKC-activation dependent (HCT116) → AP-1, Elk1, Egr1 activation → IL-8, EGFR - FAK/Src - Ca2+ release | Not described |
