Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma
Abstract
:1. Introduction
2. PODXL Expression and Regulation in Human Malignancies
3. PODXL in Cancer Cell Survival, Proliferation, and Stemness
4. PODXL in Metastasis
5. PODXL in EMT
6. PODXL in Drug Resistance
7. PODXL in Cancer Cell Metabolism
8. Conclusions and Future Perspectives
Funding
Conflicts of Interest
Abbreviations
Abb. | Full Name |
ADCC | Antibody-dependent cellular cytotoxicity |
BMI-1 | B-cell-specific Moloney murine leukemia virus integration site 1 homolog |
B-NHL | B-cell non-Hodgkin lymphoma |
CXCR4 | C-X-C motif chemokine receptor 4 |
CXCL12 | C-X-C motif chemokine ligand 12 |
EMT | Epithelial-mesenchymal transition |
FASN | Fatty acid synthase |
G6PD | Glucose-6-phosphate dehydrogenase |
GLUT3 | Glucose transporter 3 |
GSK3B | Glycogen synthase kinase-3B |
KLF4 | Kruppel-like factor 4 |
MAPK | Mitogen-activated protein kinase |
NHL | Non-Hodgkin lymphoma |
PI3K | Phosphatidylinositol 3-kinase |
PINCH1 | Particularly interesting new cysteine-histidine rich protein 1 |
PODXL | Podocalyxin |
PPP | Pentose phosphate pathway |
shRNAs | Short hairpin RNAs |
SP1 | Specific protein 1 |
TGF-beta | Transforming growth factor-beta |
WT1 | Wilms´ tumor antigen 1 |
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Survival-Proliferation-Stemness | ||||
Tumor Cell Type | Cell Line Model | Method | Biological Effect and Mechanism | Ref. |
Glioblastoma multiforme | JHU-0879 | Silencing of PODXL | Decreased proliferation and tumorsphere formation | [45] |
LN-299; U-118 MG | Ectopic overexpression of PODXL | Increased proliferation and c-MYC and c-JUN mRNA levels (by increasing beta-catenin signaling through the p38 MAPK/GSK3B pathway) | [75] | |
Silencing of PODXL | Decreased proliferation | |||
LN-299; U-118 MG | Ectopic overexpression of PODXL | Increased proliferation (by inhibiting Ang-(1-7)/Mas signaling through a PI3K dependent mechanism) | [76] | |
Silencing of PODXL | Decreased proliferation | |||
Gastric cancer | BGC823 | Ectopic overexpression of PODXL | Increased colony formation | [77] |
MGC803 | Silencing of PODXL | Decreased colony formation | ||
SGC-7901 | Ectopic overexpression of PODXL | Increased cell proliferation, colony formation and activation of PI3K/AKT, NF-kb, MAPK (through interaction with RUFY1) Decreased apoptosis | [52] | |
Silencing of PODXL | Decreased cell proliferation, colony formation and activation of PI3K/AKT, NF-kb, MAPK Increased apoptosis | |||
Ectopic overexpression of PODXL/Mouse xenograft | Increased tumor growth in vivo (through interaction with RUFY1) | |||
Silencing of PODXL/Mouse xenograft | Decreased tumorigenesis in vivo | |||
SGC-7901; AGS | Silencing of PODXL/ Mouse xenograft | Decreased tumor growth in vivo | [51] | |
Colon cancer | HCT15 | Silencing of PODXL | Decreased tumorsphere formation Decreased TAZ, survivin, CTGF, cyclinD1, and stem-cell-related gene expression | [54] |
HCT116; LOVO | Silencing of PODXL | Decreased proliferation and clonogenic potential Increased apoptosis and caspase-3 and caspase-9 expression | [78] | |
Oral squamous cell carcinoma | SAS | Silencing of PODXL | Decreased proliferation and colony formation | [46] |
HSC-2 | Silencing of PODXL | Decreased proliferation | [79] | |
Silencing of PODXL/mouse xenograft | Decreased tumor growth in vivo | |||
Breast cancer | MCF-7 | Ectopic overexpression of PODXL | Increased formation of tumorspheres | [80] |
MDA-MB-231 | Silencing of PODXL | No effect on cell proliferation under adherent culture conditions Decreased formation of tumorspheres | ||
Silencing of PODXL/Mouse xenograft | Decreased primary tumor growth, invasion and distant metastasis, in vivo | |||
MDA-MB-231 (clone 4175); NAMEC8R | Silencing of PODXL | No effect on cell proliferation under culture conditions | [81] | |
Silencing of PODXL/Mouse xenograft | No effect on primary tumor growth in vivo | |||
MCF-7 | Ectopic overexpression of PODXL | Increased formation of tumorspheres | ||
MDA-MB-231 | Silencing of PODXL | No effect on cell proliferation under culture conditions | [82] | |
Silencing of PODXL/Mouse xenograft | Decreased primary tumor growth | |||
Pancreatic cancer | SW1990; Pa03c | Silencing of PODXL/Mouse xenograft | No effect on primary tumor growth in vivo | [83] |
Burkitt lymphoma | Raji | Ectopic overexpression of PODXL | Increased proliferation and colony formation | [27] |
Metastasis | ||||
Tumor Cell Type | Cell Line Model | Method | Biological Effect and Mechanism | Ref. |
Glioblastoma multiforme | LN-299; U-118 MG | Ectopic overexpression of PODXL | Increased invasion and MMP-9 expression and activation (by inhibiting Ang-(1-7)/Mas signaling through a PI3K dependent mechanism) | [76] |
Silencing of PODXL | Decreased invasion | |||
LN-299; U-118 MG | Ectopic overexpression of PODXL | Increased invasion (by increasing beta-catenin signaling through p38 MAPK pathway) | [75] | |
Silencing of PODXL | Decreased invasion | |||
Gastric cancer | SGC-7901; AGS | Silencing of PODXL | Decreased migration and invasion Decreased expression of MMP-2 | [51] |
Silencing of PODXL/Mouse xenograft | Decreased liver metastasis, in vivo | |||
SGC-7901; AGS | Ectopic overexpression of PODXL | Increased migration and invasion | [52] | |
Silencing of PODXL | Decreased migration and invasion | |||
BGC823 | Ectopic overexpression of PODXL | Increased migration and invasion | [77] | |
MGC803 | Silencing of PODXL | Decreased migration and invasion | ||
Colon cancer | HCT116; LOVO | Silencing of PODXL | Decreased migration and invasion | [78] |
HCT15 | Silencing of PODXL | Decreased migration and invasion | [54] | |
Oral squamous cell carcinoma | SAS | Silencing of PODXL | Decreased migration and invasion Inhibition of FAK activation and filopodia and invadopodia formation | [46] |
Breast cancer | MCF-7 | Ectopic overexpression of PODXL | Perturbation of cell-cell junctions | [22] |
MCF-7 | Ectopic overexpression of PODXL | Increased collective migration in 2-D culture (dependent on ezrin) Increased collective budding and invasion in 3-D culture (dependent on actomyosin) | [84] | |
Ectopic overexpression of PODXL/Mouse xenograft | Increased collective invasion and tumor budding, in vivo | |||
MCF-7 | Ectopic overexpression of PODXL | Increased migration and invasion, matrix metalloproteinases 1 and 9 expression, MAPK and PI3K activity (by interacting with ezrin) | [85] | |
MCF-7 | Ectopic overexpression of PODXL | Increased invadopodia formation (through Rac1/Cdc42/cortactin signaling) | [82] | |
MDA-MB-231 | Silencing of PODXL | Decreased invadopodia formation | ||
Silencing of PODXL/Mouse xenograft | Decreased distant metastasis, in vivo | |||
MDA-MB-231 | Silencing of PODXL/Mouse xenograft | Decreased invasion and distant metastasis, in vivo | [80] | |
MDA-MB-231 (clone 4175); NAMEC8R | Silencing of PODXL | Decreased in vitro extravasation Decreased migration. No effect on invasion | [81] | |
Silencing of PODXL/mouse xenograft | Decreased lung metastasis, in vivo | |||
HMLER | Ectopic overexpression of PODXL | Increased in vitro extravasation | ||
Ectopic overexpression of PODXL/chick CAM assay | Increased in vivo extravasation | |||
Prostate cancer | P3C | Ectopic overexpression of PODXL | Increased migration and invasion, matrix MMP-1 and MMP-9 expression, MAPK and PI3K activity (by interacting with ezrin) | [85] |
Pancreatic adenocarcinoma | MiaPaca2; Panc1 | Silencing of PODXL | Decreased in vitro extravasation | [81] |
SW1990; Pa03c | Silencing of PODXL/Mouse xenograft | Decreased lung metastasis, in vivo | [83] | |
Lung adenocarcinoma | A549 | Silencing of PODXL | Decreased migration | [86] |
A549 | Ectopic overexpression of PODXL | Increased migration and invasion (through PI3K/AKT pathway) | [87] | |
Silencing of PODXL | Decreased migration and invasion | |||
Testicular cancer | NT-2 | Silencing of PODXL | Decreased invasion | [32] |
Burkitt lymphoma | Raji | Ectopic overexpression of PODXL | Increased migration towards CXCL12 | [27] |
EMT Process | ||||
Tumor Cell Type | Cell Line Model | Method | Biological Effect and Mechanism | Ref. |
Gastric cancer | SGC-7901; AGS | Silencing of PODXL | Decreased EMT-associated markers | [51] |
Colon cancer | HCT15 | Silencing of PODXL | Decreased EMT-associated markers | [54] |
Breast cancer | MDA-MB-231 (clone 4175); NAMEC8R | Ectopic overexpression of PODXL | No effect on EMT | [81] |
Silencing of PODXL | No effect on EMT | |||
HMLER | Ectopic overexpression of PODXL | No induction of EMT | ||
Lung adenocarcinoma | A549 | Ectopic overexpression of PODXL | Increased EMT morphological changes and markers (through PI3K/AKT pathway) | [87] |
Silencing of PODXL | Decreased EMT morphological changes and markers | |||
A549 | Silencing of PODXL | Decreased EMT morphological changes and markers | [86] | |
Resistance to Drugs | ||||
Tumor Cell Type | Cell Line Model | Method | Biological Effect and Mechanism | Ref. |
Colon cancer | HCT15 | Silencing of PODXL | Increased sensitivity to 5-fluorouracil and to irinotecan | [54] |
Osteosarcoma | MG-63; U2OS | Ectopic overexpression of PODXL | Increased resistance to cisplatin (by PI3K/AKT pathway) | [88] |
Silencing of PODXL | Increased sensitivity to cisplatin | |||
Oral tongue squamous carcinoma | SCC-4; Tca8113 | Ectopic overexpression of PODXL | Increased resistance to cisplatin (by increasing BMI-1 and FAK) | [89] |
Silencing of PODXL | Increased sensitivity to cisplatin | |||
Astrocytoma | SW1783 | Ectopic overexpression of PODXL | Increased resistance to temozolomide (by PI3K/AKT pathway) | [90] |
U-87 | Silencing of PODXL | Increased sensitivity to temozolomide | ||
Burkitt lymphoma | Raji | Ectopic overexpression of PODXL | Increased resistance to dexamethasone and obinutuzumab | [27] |
Cancer Cell Metabolism | ||||
Tumor Cell Type | Cell Line Model | Method | Biological Effect and Mechanism | Ref. |
Burkitt lymphoma | Raji | Ectopic overexpression of PODXL | Increased lipogenesis, PPP, glutaminolysis, and glutamine dependence; decreased glucose dependence | [27] |
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Tamayo-Orbegozo, E.; Amo, L.; Díez-García, J.; Amutio, E.; Riñón, M.; Alonso, M.; Arana, P.; Maruri, N.; Larrucea, S. Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma. Cancers 2020, 12, 396. https://doi.org/10.3390/cancers12020396
Tamayo-Orbegozo E, Amo L, Díez-García J, Amutio E, Riñón M, Alonso M, Arana P, Maruri N, Larrucea S. Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma. Cancers. 2020; 12(2):396. https://doi.org/10.3390/cancers12020396
Chicago/Turabian StyleTamayo-Orbegozo, Estíbaliz, Laura Amo, Javier Díez-García, Elena Amutio, Marta Riñón, Marta Alonso, Paula Arana, Natalia Maruri, and Susana Larrucea. 2020. "Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma" Cancers 12, no. 2: 396. https://doi.org/10.3390/cancers12020396