Human secreted proteins SLURP‐1 and SLURP‐2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors

Abstract

This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

Differential Expression of Nicotine Acetylcholine Receptors Associates with Human Breast Cancer and Mediates Antitumor Activity of αO-Conotoxin GeXIVA

“…α5 nAChRs are expressed in all the tested 16 breast cancer cell lines according to our results, which suggested the importance of α5 nAChRs during generation of breast tumors (Table 1). Bychkov et al and Lyukmanova et al confirmed that the expression of functional α7-nAChRs on the cancer cells membrane by confocal microscopy [8,11], suggesting that the homomeric channels that had been composed of α7 subunits are a valuable therapeutic target for cancers. The main argument was that nicotine activated α7 nAChRs can cause Ca 2+ influx into cancer cells and trigger membrane depolarization, which activates voltage-gated Ca 2+ channels and subsequently activates the MAPK pathway, which may result in inhibition of apoptosis [41,42].…”

“…The main argument was that nicotine activated α7 nAChRs can cause Ca 2+ influx into cancer cells and trigger membrane depolarization, which activates voltage-gated Ca 2+ channels and subsequently activates the MAPK pathway, which may result in inhibition of apoptosis [41,42]. Except for α7 nAChRs, the homopentameric structure of α9 nAChRs has been confirmed to play a major role in breast cancer and other cancer cells [8,11,19,34]. Over-expression and activation of the α9-containing nAChRs during tumorigenesis was discovered in human breast epithelial cells.…”

“…As described above, all the tested cell lines were found to express neuronal nAChR subunits of α3, α4, α5, α7, α9, α10, β2, β3 and β4. Moreover, previous studies showed that nAChRs play a crucial role in the course of human cancer development [11,12,32]. In order to quantify and compare the mRNA expression amounts of each nAChR subunit among human breast cancer cell lines and the normal (nonmalignant) human breast cell lines, real-time quantitative fluorescent PCR were used to detect the mRNA expression level of α3, α4, α5, α7, α9, α10, β2, β3 and β4 nAChR subunits respectively ( Figure 2).…”

“…αO-conotoxin GeXIVA that targeted α9α10 nAChR were able to significantly inhibit breast cancer cell proliferation in vitro and merits further investigation as potential agents for targeted therapy. and non-small-cell lung carcinomas (NSCLCs), head, neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers [8][9][10][11][12]. Several nAChRs subunits, including α3, α7, α9 and β4, are extensively expressed in various tumor cells and they are involved in regulation of cell proliferation, apoptosis, invasion, migration and angiogenesis [13][14][15][16].…”

Nicotinic acetylcholine receptors

“…Consistent with this model, SLURP1 and SLURP2, endogenous peptide antagonists of α7 and non‐α7 nAChRs, respectively, are reported to decrease the rate of cell proliferation in a variety of epithelial cancer cell lines, in the study of Lyukmanova et al . ().…”