6533b870fe1ef96bd12d0596
RESEARCH PRODUCT
ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis
Salvatore VieniVincenzo De LaurenziMiriam GaggianesiSimone Di FrancoAlice TurdoJan Paul MedemaTiziana ApuzzoEliana GulottaFrancesco DieliMaria Luisa ColoritoDaniela BarcaroliGiuseppe PistoneAntonina BenfanteMatilde TodaroLaura Rosa MangiapaneRaju KandimallaAurora ChinniciGiorgio Stassisubject
0301 basic medicineGene isoformEpithelial-Mesenchymal TransitionBreast Neoplasmsmedicine.disease_causeMetastasisMicePhosphatidylinositol 3-Kinases03 medical and health sciencesBreast cancerTumor MicroenvironmentmedicineAnimalsHumansmetastasisEpithelial–mesenchymal transitionNeoplasm MetastasisPI3K/AKT/mTOR pathwayAgedAged 80 and overTumor microenvironmentp63breast cancer initiating cellsbusiness.industryMembrane ProteinsCD44v6Middle Agedmedicine.diseasePI3K/AKT pathwayHyaluronan Receptors030104 developmental biologyOncologyDrug Resistance NeoplasmTumor progressionImmunologyCancer researchFemalebreast cancer initiating cellmetastasibusinessCarcinogenesisProto-Oncogene Proteins c-aktSignal TransductionPriority Research Paperdescription
P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the majority of cells within the tumor appears to express predominantly TAp63 isoform. While ΔNp63 exerts its effects by regulating a PI3K/CD44v6 pathway, TAp63 modulates this pathway in an opposite fashion. As a result, tumorigenicity and invasive capacity of breast cancer cells is a balance of the two isoforms. Finally, we found that tumor microenvironmental cytokines significantly contribute to the establishment of breast cancer cell phenotype by positively regulating ΔNp63 and CD44v6 expression.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 |