Open AccessPAX 3 in neuroblastoma: oncogenic potential, chemosensitivity and signalling pathways
Author(s) -
Fang WenHui,
Wang Qiuyu,
Li HongMei,
Ahmed Mashud,
Kumar Patricia,
Kumar Shant
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12155
Subject(s) - signalling pathways , cancer research , hedgehog signaling pathway , signalling , neuroblastoma , signal transduction , suppressor of cytokine signalling , biology , chemistry , microbiology and biotechnology , genetics , cell culture , stat3 , socs3
Transcription factor PAX 3/Pax3 contributes to diverse cell lineages during embryonic development and is important in tumourigenesis. We found that PAX 3 is re‐expressed in neuroblastoma and malignant neuroblastic (N‐type) neuroblastoma cells had significantly higher PAX 3 protein expression than their benign substrate‐adherent (S‐type) counterparts. Knock‐down of PAX 3 expression by si RNA transfection resulted in persistent cell growth inhibition in both types of neuroblastoma cell, owing to G1 cell cycle arrest and progressive apoptosis. Inhibition of PAX 3 expression significantly decreased the attachment of S‐type SH ‐ EP 1 cells to extra‐cellular matrix proteins, fibronectin, laminin and collagen IV . Migration and invasion of both neuroblastoma cell types were markedly reduced after PAX 3 down‐regulation. PAX 3 knock‐down significantly augmented the cytotoxic effect of chemotherapeutic agents, etoposide, vincristine and cisplatin, commonly used to treat neuroblastoma. Microarray analyses revealed that particularly signalling pathways involving cell cycle, apoptosis, cell adhesion, cytoskeletal remodelling and development were altered by PAX 3 down‐regulation. Changes in PAX 3 downstream genes identified by microarray analyses were validated in 47 genes by quantitative PCR . These novel findings lead us to propose that PAX 3 might contribute to oncogenic characteristics of neuroblastoma cells by regulating a variety of crucial signalling pathways.