The importance of melanoma inhibitory activity gene family in the tumor progression of oral cancer

Abstract

Oral squamous cell carcinoma has a high potential for locoregional invasion and nodal metastasis. Consequently, early detection of such malignancies is of immense importance. The melanoma inhibitory activity (MIA) gene family comprises MIA, MIA2, transport and Golgi organization protein 1 (TANGO), and otoraplin (OTOR). These members of the MIA gene family have a highly conserved Src homology 3 (SH3)-like structure. Although the molecules of this family share 34-45% amino acid homology and 47-59% cDNA sequence homology, those members, excluding OTOR, play different tumor-associated functions. MIA has a pivotal role in the progression and metastasis of melanoma; MIA2 and TANGO have been suggested to possess tumor-suppressive functions; and OTOR is uniquely expressed in cochlea of the inner ear. Therefore, the definite functions of the MIA gene family in cancer cells remain unclear. Since the members of the MIA gene family are secreted proteins, these molecules might be useful tumor markers that can be detected in the body fluids, including serum and saliva. In this review, we described the molecular biological functions of the MIA gene family in oral cancer.

Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell Carcinoma

“…However, chemokines can recruit CD4 + Th2 cells and CD4 + T regulatory (Treg) cells into the tumor microenvironment, causing inhibited CTL antitumor responses [26]. Previously, we reported that the melanoma inhibitory activity 2 (MIA2) in OSCC is promoted by a disturbance in the tumor immunity through the suppression of CTL, Th1 cells, and CD40L + and granzyme B + T lymphocytes and relative increment in Treg cells [4,27]. In addition, tumor-infiltrating myeloid cells, with the co-expressing macrophage marker CD11b and the neutrophil marker Gr1, have been reported to suppress CTL and natural killer (NK) cell activity [5].…”

“…They also inactivate tumor-suppressor genes [6]. Loss of heterozygosity (LOH) on chromosomes 3p, 9p (inactivation of p16 ), and 17p (inactivation of p53 ) correlates to early-phase oral carcinogenesis; conversely, genetic alterations on chromosomes 4q, 8p, 11q, and 13q correlates with late-phase oral carcinogenesis [4]. Recent genome-wide LOH and DNA copy-number aberration analysis revealed that regions on 4q, 8p, 9p and 11q play a vital role in the disease-specific survival of OSCC patients [57].…”

“…The expression of the MIA gene family members is reported in several malignancies [93]. Transport and Golgi organization protein 1 ( TANGO ) is one of the MIA gene family members and comprises a highly conserved Src homology 3 (SH3)-like domain [4]. TANGO could be a suppressor of the invasion and migration of malignant melanoma, colorectal cancer (CRC), and HCC [108,109].…”

“…However, the TANGO expression reportedly correlated with tumor progression, nodal and distant metastasis, and shortened disease-free survival in SCC of the esophagus, lung, and uterine cervix [93]. In OSCC, TANGO also regulated adhesion to OSCC cells, transendothelial migration, and tube formation of vascular and lymphatic vascular endothelial cells by activating the platelet-derived growth factor-β polypeptide (PDGFB) and neuropilin 2 [4,54]. Imatinib, an inhibitor of the PDGF receptor tyrosine kinase, might be useful for OSCC treatment because of decreased TANGO activity [4].…”

“…In addition, OSCC tends to cause cervical lymph node metastasis because the lymphatic vessels in the oral cavity are rich and comprise numerous anastomoses [3]. Furthermore, OSCC often causes dysfunctions in chewing and swallowing, as well as speech and esthetic disorders, which can worsen patients’ quality of life [4]. Hence, the recurrent potential of OSCC is considered to be closely associated with the local expansion and nodal metastasis of tumor cells.…”