MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma

Abstract

The incidence of recurrent t(6;9) translocation of the MYB proto-oncogene to NFIB (the gene that encodes nuclear factor 1 B-type) in adenoid cystic carcinoma (ACC) tumour tissues is high. However, MYB [the gene that encodes transcriptional activator Myb (MYB)] overexpression is more common, indicating that MYB serves a key role in ACC. The current study aimed to investigate the role of MYB in salivary (S)ACC growth and metastasis. A total of 50 fresh-frozen SACC tissues and 41 fresh-frozen normal submandibular gland (SMG) tissues were collected to measure MYB mRNA expression, and to analyse the associations between MYB and epithelial-mesenchymal transition (EMT) markers. Compared with normal SMG tissue, SACC tissues demonstrated significantly increased MYB expression, with a high expression rate of 90%. Interestingly, MYB tended to be negatively correlated with CDH1 [the gene that encodes cadherin-1 (E-cadherin)] and positively correlated with VIM (the gene that encodes vimentin), suggesting that MYB is associated with SACC metastasis. To explore the role of MYB in SACC, the authors stably overexpressed and knocked down MYB in SACC cells. The authors of the current study demonstrated that MYB overexpression promoted SACC cell proliferation, migration and invasion, whereas its knockdown inhibited these activities. Additionally, when MYB was overexpressed, CDH1 expression was downregulated, and CDH2 (the gene that encodes cadherin-2), VIM and ACTA2 (the gene that encodes actin, aortic smooth muscle) expression was upregulated. Then, the effect of MYB on lung tumour metastasis was investigated in vivo in non-obese diabetic/severe combined immunodeficiency mice. MYB overexpressing and control cells were injected into the mice through the tail vein. The results revealed that MYB promoted SACC lung metastasis. Collectively, these results demonstrated that MYB is aberrantly overexpressed in SACC tissues, and promotes SACC cell proliferation and metastasis, indicating that MYB may be a novel therapeutic target for SACC.

Hsa_circ_0015326 Promotes the Proliferation, Invasion and Migration of Ovarian Cancer Through miR-127-3p/MYB

“… 28 , 29 In recent years, many studies have also found that MYB can regulate cancer progression. 30 , 31 Zhang et al showed that MYB was highly expressed in OC and could promote epithelial–mesenchymal transition and cisplatin resistance in OC. 32 Furthermore, previous studies also indicated that MYB overexpression could promote OC proliferation, invasion and cisplatin resistance by activating NF-κB/STAT3 pathway.…”

Multicentre clinicopathological study of adenoid cystic carcinoma: A report of 296 cases

“…[19][20][21] The high expression of MYB mRNA might explain the high frequency of metastasis from tumours of the major salivary gland, especially those of the submandibular gland. 22,23 In our study, 54 (54/77) primary cases showed positivity for S100, but seven of nine metastatic cases showed negativity for S100 (7/9) (p = 0.013). A plausible reason for the lack of S100 expression is the absence of myoepithelial cells or the lack of expression of S100 proteins despite the presence of myoepithelial cells.…”

Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease

“…Myb, a membrane protein, is overexpressed in 60-80% of cases of ACCs, usually correlated with a genetic translocation of the MYB gene to the transcription factor gene NFIB, resulting in the MYB-NFIB fusion, an important oncogene (t [6,9] ). This fusion has been postulated as the main driver of tumor proliferation in ACC (87,88). A MYB oncogene fusion, through Akt and mitogenactivated protein kinase (MAPK) signaling pathways, activates the expression of NSR, MET, EGFR, IGF1R, and specifically IGF2.…”