Table 1 Gliogenic genes/signaling pathways and their role in glioblastoma development

TGF beta including BMP

Gliogenic. BMP works with SMAD in gliogensis

Inhibit G1 to S transitions and cause cytostasis.

Inhibit c-myc. BMP downregulates EGFR.

PAX6

Neurogenic but with Nkx6.1 it contributes to astrocytogenesis

Upregulated PAX6 acts as tumor suppressor

Controls VEGF, angiogenesis, and GBM invasiveness.

P300

Gliogenic, induces the cells more towards GFAP expression.

Anti-GBM. The c-myc gene overrides p300 and then GFAP, leading to upregulation of nestin

Repressor of nestin which is also involved with stemness (sox2).

NRSF/REST

Astrocytogenic. It halts neurogenesis and induces gliogenesis.

Strong proliferative response makes it capable of contributing to GBM oncogenesis.

REST amplification is also implicated in GBM. Promotes stemness in GBM.

LIF

Gliogenic. Low levels cause differentiation.

In GBM, TGF-beta signaling causes it to become pro-oncogenic.

When LIF is applied alone to cell lines, it causes growth inhibition in GBM.

HOPX

Primarily astrocytogenic

Tumor suppressor. Downregulated in GBM

It keeps NSCs in quiescent stage.

Notch

Contributes to gliogenesis but also contribute to the stemness in GBM

EGFR and Notch are interlinked and are upregulated in GBM.

NOTCH works with FGF to keep NSCs in proliferative stage. NPCs are regulated by notch signaling.

SOX9 and SOX4

Involved in gliogenesis but in GBM micro-environment lead to stemness.

Sox members are involved in reprogramming of GBM stem cells

Interacts with pathways Shh and Notch in morphogenesis.

SHH

More neurogenic than oncogenic.

In GBM, shh upregulates Hes1 and is involved in stemness.

When PTEN becomes defective in GBM, then SHH and PI3K become dysregulated.

FGFR

Gliogenic roles but in GBM development contribute to the oncogenesis.

FGFR has strong interactions with MAPK and in GBM become dysregulated

FGFR1 is expressed in neurons and FGFR2 is more expressed in gliogenic differentiation

JAK-STAT

Gliogenic. It also contributes to the stem cell maintenance.

In GBM development, it becomes oncogenic.

Vast net of interactions. It interacts with PI3K/AKT/mTOR pathway, MAPK/ERK pathway and several others.

STAT3

Gliogenic. But micro-environment also has vast effect on its role.

In GBM, STAT3 mutations make massive contributions to GBM oncogenesis.

It also interacts with EGFR which plays key role in GBM development

IL-6 family

Gliogenic.

Works with STAT3 in promoting pro-oncogenic pathways

With age, the gene expression of inflammatory cytokines increase in the body.

G FAP and S100

Involved in astrocytogenesis

Upregulated in GBM

GFAP also regulate astrocyte neuronal interactions

Hey1

Works with Notch in gliogenesis

Dysregulated Hes1 plays role in stemness and EMT induction in GBM development.

Shh also upregulates Hes1 gene expression

NF-κB

When dysregulated, harms neural stem cells (NSCs) and gliogenesis potential.

In GBM oncogenesis, it contributes to EGFR amplification.

NF-κB in GBM also contributes to EMT and GBM stemness.

Neuregulin-1

It is a gene of EGF family and contributes to astrocytogenesis.

Nrg1 and erb interact with each other and in GBM contribute to oncogenesis.

Nrg1, TGF alpha, EGFR all have profound interactions with one another and impact PI3k/AKT pathway, MAPK and JAK/STAT pathway

MAPK

Involved in gliogenesis.

In GBM, it interacts with EGFR, mTOR/PI3K/Akt, PDGFR, and RAS.

MAPK is also involved In Insulin resistance.

MEK and E2F

Involved in gliogenesis but they contribute to G1 to S transitions in GBM development.

RAS over-expresses MEK in GBM. Rb1 interacts with CDKs in inhibiting E2F.

This pathway becomes damaged in GBM and CDKs cause E2F based G1 to S transitions.

TCFL2/LEF

Involved in gliogenesis.

They have been detected in GBM samples.

These transcription factors of WNT signaling works with beta catenin.

Ephrins and Netrins

Involved in gliogenesis. Their role also includes angiogenic activity.

Their dysregulations are involved in GBM development.

NTNs contribute to GBM stemness. NTN-1 activates Notch and interacts with EGFR.

Transcription factors NFIX

NFIX TF interacts with STAT3 and is involved in gliogenesis.

NFIX works with Ezrin protein, both are dysregulated in GBM

TF NFIX regulates NPC differentiation.