title: Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and its genetic loss predicts adverse prognosis.
abstract: Protocadherin 10 (PCDH10), a novel tumor suppressor gene in human cancers, is located in a common deleted region at chromosome 4q28 in colorectal cancer (CRC). This study aimed to ascertain the genetic loss of PCDH10 and its clinical relevance in CRC and to explore the tumor suppressor function of PCDH10. The genetic deletion of PCDH10 was determined in 171 pairs of primary tumors and corresponding normal mucosae by loss of heterozygosity study. In total, 53 carcinomas were positive for allelic loss of PCDH10. The genetic aberration was significantly associated with tumor progression and distant metastasis (p = 0.021 and p = 0.018, respectively) and was an independent predictor of poor survival for CRC patients (p = 0.005). Expression of PCDH10 gene was silenced or markedly down-regulated in all of 12 CRC cell lines tested and in 41 of 53 colorectal carcinomas compared with their matched normal mucosae. Ectopic expression of PCDH10 suppressed cancer cell proliferation, anchorage-independent growth, migration and invasion in vitro. Subcutaneous injection of PCDH10-expressing CRC cells into SCID mice revealed the reduction of tumor growth compared with that observed in mock-inoculated mice. Furthermore, through intrasplenic implantation, the re-expression of PCDH10 in silenced cells restrained liver metastasis and improved survival in SCID mice. In conclusion, PCDH10 is a pivotal tumor suppressor in CRC, and the loss of its function promotes not only tumor progression but also liver metastasis. In addition, the genetic deletion of PCDH10 represents an adverse prognostic marker for the survival of patients with CRC.
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Jao
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tsai
authors.forename: Hoi-Yan
authors.initials: HY
authors.lastname: Lio
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Weng
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Sheng-Tai
authors.initials: ST
authors.lastname: Tzeng
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Chang
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Lai
authors.forename: Sou-Jhy
authors.initials: SJ
authors.lastname: Yen
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.forename: Ya-Chien
authors.initials: YC
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D009367:Neoplasm Staging; D011379:Prognosis; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; C438603:PCDH10 protein, human; D000091363:Protocadherins; D012333:RNA, Messenger
keywords: PCDH10; colorectal cancer; liver metastasis; loss of heterozygosity; prognostic marker