Targeting the Osteopontin-regulated PI3K/AKT signaling pathway: A molecular approach to overcome drug resistance and metastasis in gastrointestinal tumors

Table 2 Core mechanisms of Osteopontin-phosphatidylinositol 3-kinase/protein kinase B axis in malignant progression

Mechanistic category	Key molecules/pathways	Functional outcomes	Associated cancers
Promotion of proliferation & survival	Integrin receptors, BAD/Bcl-2, PI3K/AKT/mTOR	Inhibition of apoptosis; Upregulation of MMP-2/VEGF; Enhanced cell survival	GC, pancreatic cancer
Induction of EMT & metastasis	E-cadherin, Snail, Twist, EGFR/PI3K/AKT	Loss of epithelial markers; Activation of mesenchymal programs; Enhanced invasiveness	HCC, NSCLC
Remodeling tumor microenvironment	CAFs, VEGF, IL-8, CXCL11/POSTN	Angiogenesis; Immune suppression; CSC enrichment; Stromal activation	GC, colorectal cancer

PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; mTOR: Mechanistic target of rapamycin; EGFR: Epidermal growth factor receptor; CAFs: Cancer-associated fibroblasts; VEGF: Vascular endothelial growth factor; CXCL11: C-X-C motif chemokine ligand 11; POSTN: Periostin; EMT: Epithelial-mesenchymal transition; MMP-2: Matrix metalloproteinase 2; CSC: Cancer stem cells; NSCLC: Non-small cell lung cancer; GC: Gastric cancer; HCC: Hepatocellular carcinoma.