Table 1.
Role of stromal cells in promoting EMT in different cancer types.
| Stromal Affect | Type of Regulation | Targets on Cancer Cells | Role in Cancer Cells | References’ Number | Cancer Types |
|---|---|---|---|---|---|
| Integrin B1 | Direct binding | Wnt/B catenin | [11] | Acute Lymphoblastic leukemia ALL | |
| TGF-b | Secreted factor | SMAD | Promote EMT | [14] | Breast cancer Ovarian cancer Gastric cancer Prostate cancer Renal cancers |
| FGF | Secreted factor | E-cadherin | Promote EMT | [14] | Ovarian cancer |
| EGF | |||||
| HGF | Cell–cell adhesion | ||||
| Conditioned media | Secreted factors | AMPK/mTOR | Suppress the expression of E-cadherin/ increase vimentin expression | [15,16] | Colorectal cancer |
| Wnt signaling | Promote nuclear translocation of B-catenin | [17] | Cholangiocarcinoma cell lines QBC939 | ||
| Collagen deposition | ECM remodeling | Upregulation of SLUG and SNAIL | Direct interaction of collagen IV with integrins a1b1 and a2b1 | [29,30] | Ovarian cancer Hepatocellular carcinoma |
| MMPs | ECM remodeling | Provide synergistic EMT signals | Enrich cancer cell stemness, and promote epithelial and tumor cell proliferation | [33,34,35,36,37,38] | Ovarian cancer Breast cancer |
| lysyl oxidases | Increased ECM stiffness | Stimulate EMT via mechanosenstation | [39] | Breast cancer | |
| Lactate | Secreted | TGF-b activation | Induce EMT | [68] | Prostate cancer |
| TGF-b2 | Secreted factor | CD36 | Promote FAO by increasing fatty acid uptake | [73] | |
| Acidosis | TME | Promote autocrine TGF-b2 signaling | Induce partial EMT | [73] | |
| TGF-b1 | Secreted factor | Downregulate chREBP | Decrease fatty acid synthesis and promote fatty acid oxidation during EMT | [75] | Lung A549 cells |
| TGF-b | Secreted factor | Upregulation of GLUT1 | Increase glucose uptake | [81,82,83,84,85] | Gastric cancer Pancreatic ductal adenocarcinoma Glioma Breast cancer |
| TGF-b | Secreted factor | Upregulation of GLUT3 | Increase glucose uptake | [86] | Non-small cell lung carcinoma |
| PFKFB3 | Promote glycolysis | Panc1 PDAC cells | |||
| CPT1A | Overexpression in tumor cells | Vimentin, SNAIL, E-cadherin | Increase vimentin and SNAIL expression, decrease E-cadherin expression, enhance EMT phenotype | [110] | Gastric cancer Pancreatic ductal Adenocarcinoma Glioma Breast cancer |
| FABP12 | Amplification in tumor cells | Induce EMT via PPARy and concurrent FAO | [112] | Prostate cancer | |
| IL6 | Secreted | CD133 | Drive glycolytic flux and enhance malignant potential by enriching stemness | [114] | Pancreatic cancer |
| IL6, CXCL10 CCL5 | Secreted | PGM1 activation | Upregulate glycogen metabolism to drive EMT and metastasis | [115,116] | |
| CRMP2 | Secreted | HIF1A | Drive EMT via upregulation of glycolysis | [117] | Ovarian cancer |