New advances of TMEM88 in cancer initiation and progression, with special emphasis on Wnt signaling pathway.
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. Highlights Wnt 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.
Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, China.|School of Pharmacy, Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China.
Yun-Xuan
YX
Ge
Department of Cardiology, First Affiliated Hospital of Anhui Medical University, Hefei, China.|School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Chang-Hui
CH
Wang
The Second People's Hospital of Hefei & Affiliated Hospital of Medical University of Anhui, Hefei, China.
Fu-Yong
FY
Hu
School of Life Sciences, Anhui Medical University, Hefei, China.
Lin-Xin
LX
Pan
Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Jie
J
Min
Department of Otolaryngology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Kai-Yuan
KY
Niu
School of Pharmacy, Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China.
Lei
L
Zhang
School of Pharmacy, Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China.
Jun
J
Li
School of Pharmacy, Institute for Liver Diseases of Anhui Medical University, Anhui Medical University, Hefei, China.
Tao
http://orcid.org/0000-0001-7395-0451
T
Xu
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D000072261:Dishevelled Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D060449:Wnt Signaling Pathway
D000072261:Dishevelled Proteins; D008565:Membrane Proteins; C555652:TMEM88 protein, human
TMEM88; Wnt signalling pathway; cancer; cancer therapy; β-catenin