The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers.
OBJECTIVE
Metastasis remains the main cause of death in both bladder (BCa) and prostate (PCa) cancers. The results of chemotherapy did not show any significant improvement of the survival the past years. Cancer research has led to the identification of signaling pathways involved and molecular targets that could change the natural history. The epithelial-mesenchymal transition (EMT), critical during embryonic development, becomes potentially destructive in many epithelial tumors progression where it is inappropriately activated. The cell-cell and cell-extracellular matrix interactions are altered to release cancer cells, which are able to migrate toward metastatic sites. Hallmarks of EMT include the down-regulation of E-cadherin expression, which is the main component of the adherens junctions. The protein TWIST is a transcriptional repressor of E-cadherin, tumor progression, and metastasis, and could be used as a molecular target to restore the chemosensitivity in BCa and PCa.


METHODS
We selected the last 5-year basic research literature on EMT and TWIST but also clinical studies on BCa and PCa in which TWIST is overexpressed and could be considered as an efficient prognostic marker and molecular target.


RESULTS
TWIST is considered as a potential oncogene promoting the proliferation and inhibiting the apoptosis. TWIST promotes the synthesis of the pro-angiogenic factor, vascular endothelial growth factor (VEGF) involved in tumor progression and metastasis. Apoptosis and angiogenesis are two essential cancer progression steps in many epithelial tumors, including BCa and PCa.


CONCLUSIONS
With the targeted therapy, oncology has entered into a new era, which is going to be critical in cancer treatment in combination with traditional anticancer drugs.
Wallerand
Hervé
H
Department of Urology, Centre Hospitalo-Universitaire Pellegrin-Tripode, Victor Segalen School of Medicine, Bordeaux, France. herve.wallerand@chu-bordeaux.fr
Robert
Grégoire
G
Pasticier
Gilles
G
Ravaud
Alain
A
Ballanger
Philippe
P
Reiter
Robert E
RE
Ferrière
Jean-Marie
JM
D017209:Apoptosis; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000209:etiology; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D015398:Signal Transduction; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1