Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P42345 (
mTOR
)
26,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer characterized by aggressive local invasion and metastasis. The pathogenesis of OSCC is mainly due to the accumulation of genetic alterations in epithelial cells, but the underlying mechanism for its development remains unclear. Here, we found that the expression level of
regulator of G protein signaling 12
(
RGS12
) was significantly reduced in human OSCC. To understand the role and mechanism of
RGS12
in OSCC, we generated a novel
RGS12
global knockout (CMV
Cre/+
;
RGS12
fl/fl
) mouse model by crossing
RGS12
fl/fl
mice with CMV-Cre transgenic mice and then further induced the mice to develop OSCC by using 4-nitroquinoline 1-oxide (4NQO). Deletion of
RGS12
exhibited aggressive OSCC in the tongue compared with the control
RGS12
fl/fl
mice. Knockdown of
RGS12
in OSCC cells significantly increased cell proliferation and migration. Mechanistically, we found that
RGS12
associated with phosphatase and tension homolog (PTEN) via the PDZ domain to upregulate the phosphorylation and SUMOylation of PTEN and then correspondingly inactivated the AKT/
mTOR
signaling pathway. To test the potential therapeutic effect of
RGS12
on OSCC, we overexpressed
RGS12
in OSCC cells and found a significant inhibition of cancer cell proliferation and migration. Moreover, subcutaneous inoculation of
RGS12
-overexpressed OSCC cells in NOD scid mice showed a significant reduction in tumor formation. Our findings reveal that
RGS12
is an essential tumor suppressor and highlights
RGS12
as a potential therapeutic target and prognostic biomarker of OSCC.
...
PMID:RGS12 Represses Oral Cancer via the Phosphorylation and SUMOylation of PTEN. 3319 57
