title: The role of ELK3 to regulate peritumoral lymphangiogenesis and VEGF-C production in triple negative breast cancer cells.
abstract: Tumor-induced lymphangiogenesis, a major conduit for cancer cell dissemination from the primary tumor site to lymph nodes and beyond, eventually leads to metastasis in cancer patients. Given the recent evidence revealing that the suppression of ELK3 inhibits the metastasis of triple-negative breast cancer cells, we aimed to study the underlying mechanism of impaired metastasis in ELK3-suppressed MDA-MB-231 cells (ELK3 KD) with regard to lymphangiogenesis. We found that the secretome of ELK3 KD cells inhibited tube formation, whereas it promoted the migration and invasion of lymphatic endothelial cells (LECs) in vitro. In vivo analysis revealed that peritumoral lymphatic vessels were not developed around the xenografted tumors of ELK3 KD. We further revealed that the suppression of NF-κB signaling in ELK3 KD was the primary cause of the reduced VEGFC expression. Taken together, we suggest that ELK3 is an upstream regulator of the NF-κB signaling pathway, the inhibition of which leads to the suppression of peritumoral lymphatic vessel development, possibly due to a low VEGFC expression.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
authors.forename: Nuri
authors.initials: N
authors.lastname: Oh
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
authors.forename: Ji-In
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea.
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, South Korea. Electronic address: kspark@cha.ac.kr.
authors.forename: Kyung-Soon
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
chemical_list: C527883:Elk3 protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D042582:Vascular Endothelial Growth Factor C
keywords: CXCL12; Elk3; Lymphangiogenesis; MDA-MB-231; NF-κB; VEGFC