Transmembrane protein 88 exerts a tumor-inhibitory role in thyroid cancer through restriction of Wnt/β-catenin signaling

Transmembrane protein 88 (TMEM88) has emerged as a newly discovered cancer-related protein that acts as a cancer-promoting or cancer-inhibiting regulator in multiple tumor types. However, the exact role of TMEM88 in thyroid cancer is undetermined. The current study was designed to determine the expression, function, and potential underlying mechanism of TMEM88 in thyroid cancer. Our data demonstrated low TMEM88 expression in thyroid cancer tissues. Decreased TMEM88 expression was also found in several thyroid cancer cell lines, and restoration of TMEM88 markedly suppressed the proliferation, colony formation, and invasive potential of thyroid cancer cells. On the contrary, TMEM88 depletion significantly accelerated the proliferation, colony formation, and invasion of thyroid cancer cells. Further experiments documented that TMEM88 overexpression markedly decreased the expression of the active form of β-catenin and inhibited the expression of Wnt/β-catenin signaling targets genes, such as c-myc and cyclin D1. Notably, reactivation of Wnt/β-catenin signaling by transfecting a vector that expressed constitutively active β-catenin partially reversed the TMEM88-mediated suppressive effect on thyroid cancer cell proliferation and invasion. In addition, TMEM88 upregulation markedly retarded the tumor growth of thyroid cancer cells in vivo using xenograft models associated with downregulation of active β-catenin expression. Taken together, our findings demonstrated that TMEM88 overexpression impeded the proliferation and invasion of thyroid cancer cells through downregulation of Wnt/β-catenin signaling. These data indicate a potential tumor-suppressive function of TMEM88 in thyroid cancer. Our study highlights a key role for TMEM88 in regulating Wnt/β-catenin signaling during the progression of thyroid cancer and suggests that TMEM88 is an attractive anticancer target for thyroid cancer.