We used immunohistochemistry to examine Rab18
protein expression in 112 cases of
HNSCC specimens. We overexpressed and knockdown Rab18 in FaDu and Detroit562
cancer cell lines. Biological roles and mechanisms of Rab18 were examined using MTT, colony formation,
Matrigel invasion assay, Western blotting,
Annexin V and JC1 staining.
RESULTS: Rab18 was upregulated in 45/112 (40.2%) cases of
HNSCC tissues, which correlated with advanced T classification, positive nodal
metastasis and
tumor node
metastasis (TNM) stage. The Oncomine and The
Cancer Genome Atlas (TCGA) analyses indicated that Rab18 was elevated in human
HNSCC tissues and correlated with poor patient survival. Functionally, Rab18 overexpression increased growth rate, colony numbers, cell cycle progression and invading ability in FaDu cells. Rab18 downregulated
cisplatin-induced apoptosis and upregulated the mitochondrial membrane potential (Δψm). Western blot revealed that Rab18 overexpression induced epithelial-to-mesenchymal transition, with downregulation of
E-cadherin and upregulation of
N-cadherin,
Vimentin and Twist. Rab18 overexpression also upregulated
Survivin protein and Rab18 knockdown showed the opposite effects on these
proteins. Treatment of STAT3 inhibitor, SH-4-54, inhibited cell invasion, increased
E-cadherin and downregulated
N-cadherin, Twist and Survivin. SH-4-54 also abolished the effects of BCAT1 on these
proteins, as well as cell invasion.
CONCLUSION: In summary, our data showed that Rab18 was overexpressed in human
HNSCC and functioned as an
oncoprotein. Rab18 regulated
HNSCC cell proliferation, invasion and
cisplatin sensitivity through STAT3 signaling in
HNSCC.