title: Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation.
abstract: NLBP (novel LZAP-binding protein) was recently shown to function as a tumor suppressor capable of inhibiting the NFκB signaling pathway. NLBP is also known as a negative regulator of cell invasion, and its expression is reduced in several cancer cell lines that have little invasive activity. Although these phenomena suggest that NLBP may be a potential tumor suppressor, its role as a tumor suppressor in human lung cancer is not well established. In contrast to our expectation, NLBP was highly expressed in the early stage of lung adenocarcinoma tissues, and overexpression of NLBP promoted proliferation of H1299 lung adenocarcinoma cells. We also found that p120 catenin (p120ctn) was a novel binding partner of NLBP, and that NLBP binds to the regulatory domain of p120ctn, and p120ctn associates with N-terminal region of NLBP, respectively. This binding leads to p120ctn stability to inhibit proteasomal degradation of p120ctn by inhibiting its ubiqutination. In addition, we also found that overexpression of NLBP and p120ctn in human lung cancer are closely related with adenocarcinoma compared with squamous cell carcinoma. Taken together, our findings reveal that NLBP is highly overexpressed in human lung adenocarcinoma, and that overexpression of NLBP promotes the cell proliferation of lung adenocarcinoma through interacting with p120ctn and suggest that NLBP may function as an oncogene in early stage carcinogenesis of lung adenocarcinoma.
authors.affiliation: Department of Biological Sciences; Sungkyunkwan University; Suwon, Republic of Korea.
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Hae-Seong
authors.initials: HS
authors.lastname: Nam
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Han
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Nam Soo
authors.initials: NS
authors.lastname: Lee
authors.forename: Suk Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Hojoong
authors.initials: H
authors.lastname: Kim
authors.forename: Jeong Seon
authors.initials: JS
authors.lastname: Ryu
authors.forename: Junhye
authors.initials: J
authors.lastname: Kwon
authors.forename: Hongtae
authors.initials: H
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D051177:Catenins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000502:physiology*; D054875:Ubiquitination; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D044767:Ubiquitin-Protein Ligases; C587954:UFL1 protein, human; D000095002:Delta Catenin; C000722347:CTNND1 protein, human
keywords: NLBP; cancer; cell proliferation; p120 catenin; ubiquitination