New advances of TMEM88 in cancer initiation and progression, with special emphasis on Wnt signaling pathway

Abstract

Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane.Recent studies showed that TMEM88 was involved in the regulation of several types of cancer.TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (β-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway. Wnt signaling pathway has been known to play important roles in many diseases, especially in cancer. For instance, hepatocellular carcinoma (HCC) has become one of the most common tumors harboring mutations in the Wnt signaling pathway. As the inhibitor of Wnt signaling, TMEM88 has been considered to act as an oncogene or a tumor suppressor. Up-regulated TMEM88 or gene therapy approaches could be an effective therapeutic approach against tumor as TMEM88 inhibits Wnt signaling through direct interaction with DVL. Here, we review the current knowledge on the functional role and potential clinical application of TMEM88 in the control of various cancers. HighlightsWnt signaling displays an important role in several pathogenesis of cancer.Wnt signaling pathway is activated during cancer development.TMEM88 has an impact on cancer by inhibiting canonical Wnt signaling.We discuss the importance and new applications of TMEM88 in cancer therapy. K E Y W O R D Sβ-catenin, cancer, cancer therapy, TMEM88, Wnt signalling pathway Abbreviations: 1,25(OH)2D3, 1,25-Dihydroxyvitamin D3; AKT/mTOR, protein kinase B/the mammalian target of rapamycin; ATF2, Activating transcription factor 2; BC, breast cancer; CBE, clinical breast exam; CIZ1b, b-variant form of CIZ1; CK1, casein kinase 1; CRD, cystein-rich domain; CTNNB1, catenin β1; Dnmt3a, DNA (cytosine-5)-methyltransferase 3A; DVL, dishevelled; EMT, epithelial-mesenchymal transition; FAK, focal adhesion kinase; FZD, frizzled; GSK3β, glycogen synthase kinase 3β; HCC, hepatocellular carcinoma; HSCs, hematopoietic stem cells; IDCs, invasive ductal carcinomas; LC, lung cancer; LRP5, low density lipoprotein receptor-related protein-5; METTL13, methyltransferase like 13; MMP-7, matrix metalloproteinase-7; MRI, magnetic resonance imaging; NSCLC, nonsmall cell lung cancer; OC, ovarian cancer; P38, protein 38; PFS, progression-free survival; TCF/LEF, T cell factor/lymphoid enhancer factor; TCGA, the cancer genome atlas; TMEM88, transmembrane protein 88; TNBC, triple-negative breast cancer; VWV, Val-Trp-Val; Zo-1, tight junction protein 1.Yun-xuan Ge, Chang-hui Wang, and Fu-yong Hu have contribute equally to this work.

Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells

“…The Wnt/b-catenin signalling is a highly evolutionary conserved pathway that is implicated in many vital biological processes, such as embryonic development, stem cell regeneration, tissue homeostasis and cell survival [18][19][20]. Studies have shown Wnt/b-catenin signalling is often upregulated in a variety of cancer, which endows cells with a stem-like phenotype that enhances self-renewal ability, multi-differential potential, and induces epithelial-to-mesenchymal transition of cancer cells [21].…”

Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer (Review)

“…FJ9, a soluble Fzd7 peptide inhibitor, disrupts the interaction between Fzd7 and Dvl (39). TMEM88 inhibits WNT signaling through direct interaction with Dvl (53). The organic molecule NSC668036 that binds to and blocks the PDZ domain of Dvl also inhibits WNT signaling (54).…”

Identification of a Methylation-Driven Gene Panel for Survival Prediction in Colon Cancer

“…In our study, hypermethylation of ARHGDIB is a favorable prognostic factor, in agreement with previous ndings in colon cancer. TMEM88 is a transmembrane protein and functions as an inhibitor of Wnt signaling [51]. TMEM88 promoter hypomethylation is associated with platinum resistance in ovarian cancer [52].…”