title: LRIG1, a 3p tumor suppressor, represses EGFR signaling and is a novel epigenetic silenced gene in colorectal cancer.
abstract: Downregulation of LRIG1 was found in many types of cancer. However, data concerning the possible mechanism of LRIG1 reduction in cancers were not reported yet. To analyze the regulation and function of LRIG1 in colorectal cancer (CRC), 6 cell lines, 46 paired tissues from primary CRC cases were employed in this study. In CRC cell lines, under-expression of LRIG1 was correlated with promoter region hypermethylation, and restoration of LRIG1 was induced by 5-Aza-2'-deoxyazacytidine treatment. Subsequently, we ectopically expressed LRIG1 in LRIG1 low-expressing HCT-116 cells and suppressed LRIG1 in LRIG1 high-expressing LoVo cells. We found that over-expression of LRIG1 inhibits cell proliferation and colony formation and tumor growth, while knockdown of LRIG1 promotes cell proliferation and colony formation. Decreased and increased EGFR/AKT signaling pathway may partially explain the lower and higher rates of proliferation in CRC cells transfected with LRIG1 cDNA or shRNA. In clinical samples, we compared the methylation, mRNA and protein expression of LRIG1 in samples of CRC tissues. A significant increase in LRIG1 methylation was identified in CRC specimens compared to adjacent normal tissues and that it was negatively correlated with its mRNA and protein expression. In conclusion, LRIG1 is frequently methylated in human CRC and consequent mRNA and protein downregulation may contribute to tumor growth by activating EGFR/AKT signaling.
authors.affiliation: Department of Oncological Surgery, The Central Hospital of Xuzhou City, Xuzhou, Jiangsu 221000, China. Electronic address: chkoukou@hotmail.com.
authors.forename: Changhua
authors.initials: C
authors.lastname: Kou
authors.affiliation: Department of Gastroenterology, The Central Hospital of Xuzhou City, Xuzhou, Jiangsu 221000, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Oncological Surgery, The Central Hospital of Xuzhou City, Xuzhou, Jiangsu 221000, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Oncological Surgery, The Central Hospital of Xuzhou City, Xuzhou, Jiangsu 221000, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China. Electronic address: qianhaixin@hotmail.com.
authors.forename: Haixin
authors.initials: H
authors.lastname: Qian
mesh_terms: D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C484445:LRIG1 protein, human; D008562:Membrane Glycoproteins; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
keywords: Colorectal cancer; EGFR signaling; LRIG1; Methylation; Proliferation