Table 2 Related neurogenic genes/signaling pathways and their role in GBM oncogenesis

Ngn1

Involved in neurogenesis

In GBM, its expression causes mitotic arrest

It prevents gliogenesis and promotes neuronal differentiation.

NeuroD

Involved in neuronal differentiation.

In GBM, its induced gene expression also blocks the proliferation.

Their upregulation causes arrest of cell cycle in GBM cells.

BMP

Involved in both gliogenesis and neurogenesis

BMP upregulation is considered to play role in halting GBM progression

Play a major role in switching NSCs towards astrocytogenesis

PAX6

Neurogenic but with Nkx6.1 it contributes to astrocytogenesis

Upregulated PAX6 acts as tumor suppressor

Controls VEGF, angiogenesis and GBM invasiveness.

Numb

Numb gene negates Notch signaling and contributes to neuronal differentiation.

Upregulation halts GBM growth and progression. Highly upregulated in mesenchymal GBM cells

But still its tumor suppressor role is controversial

Nkx6.1

Neurogenic.

It suppresses tumor development and metastasis

PAX6 is neurogenic in development but with Nkx6.1 it contributes to astrocytogenesis

ASCL1

Strongly neurogenic

It also suppresses oncogenesis in GBM cells

In GBM, it switches the cells towards neuronal cell fate

Ebf

Neurogenic.

Its loss in GBM contributes to oncogenesis

EBF3 downregulates the gene expression of proliferation and survival related genes.

Myt1

Neurogenic transcription factor

In GBM, its expression is involved in downregulating proliferation.

Low Myt1 expression is involved in glioblastoma.

PDGF and NT3

Both are neurogenic

In GBM landscape, they play oncogenic role.

PDGFR expression is increased in all grades of glioma. NT3 upregulated.

Pax7

CNS neural progenitor marker

Pax7 becomes upregulated in GBM with PTEN deficiency.

Pax7 is involved in GBM invasiveness and oncogenic transformation of NSCs.

Dbx2

CNS neural progenitor marker

High DBX2 in GBM is linked with low survival.

Dbx2 works with REST in GBM proliferation.

Hes6

Neurogenic

Upregulated in GBM. Interacts with p53, NF-κB and c-myc.

Involved in angiogenesis, proliferation and migration.

Runx1 and Runx2

Neurogenic

In GBM, there role is oncogenic.

Oncosuppressive role is controversial.

Wnt

It is kept in check by tumor suppressors and is more involved in neurogenesis.

Dysregulated wnt signaling causes activation of CyclinD1 and c-myc, causing G1 to S phase transition

It also contributes to epithelial to mesenchymal transitions.

GSK3beta

In normal cells, it acts as negative regulator of epithelial-mesenchymal-transitions (EMTs) and many proto-oncogenes

Dysregulated GSK3beta is oncogenic.

In GBM, dysregulated GSK3-beta also acts to downregulate BMP that has significant gliogenic roles

Myc

It is also involved in neurogenesis but is oncogenic in GBM development

The myc gene overrides p300 and then GFAP, leading to upregulation of nestin. This plays very important role in GBM oncogenesis.

GSK3beta also works with PI3K/FGF signaling pathway and contributes to stability of c-Myc.

SOX2 and Sox4

Regulation and maintenance of neural stem cells

In GBM, stemness is mediated by SOX2 and SOX4

Nanog, oct4, myc, they are also major contributors to GBM stemness

Klf4

Contributes to neurogenesis and pluripotency.

Acts like an oncogene in GBM

Klf4 is involved in GBM heterogeneity and GBM stem cells development.

TLX TF

One of the key regulators of NSCs maintenance

In GBM, it leads to the progression of oncogenesis

It inhibits TGF-beta as TGF beta causes cytostasis.

Oct4

Involved in pluripotency and stemness

Its expression is several folds upregulated in GBM

Without FGF signaling, the NPCs can revert back to ESCs like state with predominant oct-4 expression.

Notch/STAT3-Ser/Hes3 Axis

Neurogenic axis. Regulator of NSCs.

In GBM, it impacts the cascades of downstream signaling pathways.

It is also linked to cancer development and diabetes type 2.