PT - JOURNAL ARTICLE AU - Norihiro Kotani AU - Arisa Yamaguchi AU - Tomoko Ohnishi AU - Ryusuke Kuwahara AU - Takanari Nakano AU - Yuka Nakano AU - Yui Ida AU - Takayuki Murakoshi AU - Koichi Honke TI - Proximity proteomics identifies cancer cell membrane <em>cis</em>-molecular complex as a potential cancer target AID - 10.1101/455501 DP - 2018 Jan 01 TA - bioRxiv PG - 455501 4099 - http://biorxiv.org/content/early/2018/10/29/455501.short 4100 - http://biorxiv.org/content/early/2018/10/29/455501.full AB - Cancer-specific antigens expressed in the cell membrane have been used as targets for several molecular targeted strategies in recent years with remarkable success. To develop more effective cancer treatments, novel targets and strategies for targeted therapies are needed. Here, we examined the cancer cell membrane-resident “cis-bimolecular complex” as a possible cancer target (cis-bimolecular cancer target: BiCAT) using proximity proteomics, a technique that has attracted attention in recent years. BiCATs were detected using a previously developed method, termed the enzyme-mediated activation of radical source (EMARS), to label the components proximal to a given cell membrane molecule. EMARS analysis identified some BiCATs, such as close homolog of L1 (CHL1), fibroblast growth factor 3 (FGFR3) and α2 integrin, which are commonly expressed in mouse primary lung cancer cells and human lung squamous cell carcinoma cells. Analysis of cancer specimens from 55 lung cancer patients revealed that approximately half of patients were positive for these BiCATs. In vitro simulation of effective drug combinations used for multiple drug treatment strategy was performed using reagents targeted to BiCAT molecules. The combination treatment based on BiCAT information moderately suppressed cancer cell proliferation compared with single administration, suggesting that the information about BiCATs in cancer cells is profitable for the appropriate selection of the combination among molecular targeted reagents. Thus, BiCAT has the possibility to make a contribution to several molecular targeted strategies in future.