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Abstract

Primitive neuroectodermal tumors (PNETs) are composed of immature neuronal precursor cells and sometimes more mature neuronal cell types. Medulloblastomas, occuring in the cerebellum, represent the most common PNET and are broadly classified into two subgroups: classical and desmoplastic. Desmoplastic medulloblastomas exhibit a slightly better prognosis than classical medulloblastomas. However, there are currently no good molecular markers available to distinguish clinical outcome and similar treatment is used for most patients with associated complications. It has been shown that neoplastic cells in these tumors recapitulate stages in maturation of normal human neuroblasts; therefore, embryological studies of the earliest events in the development of the cerebellum may provide useful information about the molecular behavior of the tumor. Transcription factors such as Sox proteins involved in neural development may also play a role in the etiology of brain tumors. Sox4 in particular has been implicated in the biology of several other types of cancer. We have studied the expression of Sox4, and the closely related Sox11 gene, in medulloblastomas. Sox4 and Sox11 were strongly expressed in most classical medulloblastomas but only weakly in desmoplastic medulloblastomas. The expression profile of these two genes in developing cerebellum was also analyzed. Our results suggest that strong Sox4 and Sox11 expression in classical medulloblastomas reflects their maturation-dependent expression during normal cerebellum development, and that they may therefore provide markers to divide tumors into clinically relevant subgroups.

Distinct cellular origin and genetic requirement of Hedgehog-Gli in postnatal rhabdomyosarcoma genesis

“…SoxC transcription factors are essential for embryonic mesenchymal progenitor survival [63]. Sox4 or Sox11 up-regulation has also been implicated in hematopoietic and non-hematopoietic malignancies [55-58, 64]. Our data are the first to link the SoxC factors to eRMS and Hh-dependent tumorigenesis.…”

Identification of differentially expressed and developmentally regulated genes in medulloblastoma using suppression subtraction hybridization

“…A downstream effector of Wnt signaling along with LEF-1, SOX4 may play a role in tumor cell differentiation. SOX4 is known to be overexpressed in MB, especially the classic variant and has been suggested as a favorable prognostic factor (Lee et al, 2002).…”

TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer

“…Reduction of miR-335 levels in breast cancer cells led to increased expression of SOX4, resulting in metastatic progression as a result of increased cell invasion and migration. Subsequent to its discovery as a mediator of breast cancer metastasis, SOX4 expression has been shown to be also increased in other cancer types, including leukemia (10,11), glioblastoma (12,13), medulloblastoma (14,15), hepatocellular carcinoma (HCC) (16), and prostate cancer (17–19). Despite this evidence supporting the tumorigenic properties of SOX4, comparative analyses of the SOX4 transcriptional network revealed a high degree of variation between the target genes in different cancers, which suggest the tumor-specific and context-dependent mechanisms of target gene selection (20).…”