Potential roles of synaptotagmin family members in cancers: Recent advances and prospects

Abstract

With the continuous development of bioinformatics and public database, more and more genes that play a role in cancers have been discovered. Synaptotagmins (SYTs) are abundant, evolutionarily conserved integral membrane proteins composed of a short N-terminus, a variable linker domain, a single transmembrane domain, and two C2 domains, and they constitute a family of 17 isoforms. The synaptotagmin family members are known to regulate calcium-dependent membrane fusion events. Some SYTs play roles in hormone secretion or neurotransmitter release or both, and much evidence supports SYTs as Ca2+ sensors of exocytosis. Since 5 years ago, an increasing number of studies have found that SYTs also played important roles in the occurrence and development of lung cancer, gastric cancer, colon cancer, and other cancers. Down-regulation of SYTs inhibited cell proliferation, migration, and invasion of cancer cells, but promoted cell apoptosis. Growth of peritoneal nodules is inhibited and survival is prolonged in mice administrated with siSYTs intraperitoneally. Therefore, most studies have found SYTs serve as an oncogene after overexpression and may become potential prognostic biomarkers for multiple cancers. This article provides an overview of recent studies that focus on SYT family members’ roles in cancers and highlights the advances that have been achieved.

Identification of SYT10 as a potential prognostic biomarker in esophageal cancer by comprehensive analysis of a mRNA-pseudogene/lncRNA-miRNA ceRNA network

“…There is not much evidence of SYT10 taking any major part in cancer proliferation and cellular pathway regulation leading to tumorigenesis, but as previous studies suggest (Tsutsui et al, 2015;Zhu et al, 2021;He et al, 2022), SYT10, as a syanptotagmin family member, may play a role in drug resistance in ESCA and thus contribute to poor survival and prognosis. A detailed recent review study on potential roles of SYT family members in cancers has been properly described elsewhere (Suo, Xiao and Wang, 2022).…”

Comprehensive identification of onco-exaptation events in bladder cancer cell lines revealed L1PA2-SYT1 as a prognosis-relevant event

“…SYT1 protein is a member of the synaptotagmin family and is a membrane transport protein consisting of an N terminus, a variable link domain, a single transmembrane domain, and two C2 domains (C2A, C2B), with C2 domains serving as Ca 2+ -binding sites. 34 Overexpression of SYT1 was found to promote the invasion and metastasis ability of colon cancer cell lines in vitro . We found that L1PA2-SYT1 was the most frequent event in bladder cancer cell lines and was associated with poor prognosis in patients, and in vitro overexpression of L1PA2-SYT1 enhances the invasion capability of bladder cancer cell line, suggesting the potential tumor-driving role and clinical application potential of L1PA2-SYT1.…”

Emerging therapeutic approaches for peritoneal metastases from gastrointestinal cancers

“…Three of them in particular, isoforms VII, VIII, and XIII, have been found to play an important role in the onset and progression of gastric, colon, and other cancers. 128 This makes them a promising therapeutic target for treating PM. Studies showed that synaptotagmin XIII ( SYT13 ) plays a role in the spread of gastric cancer and among patients with recurrent or PM expressing significantly higher levels of SYT13 than those in stage I.…”