Details

Autor(en) / Beteiligte

• Jao, Tzu‐Ming
• Tsai, Ming‐Hong
• Lio, Hoi‐Yan
• Weng, Wei‐Ting
• Chen, Chun‐Chieh
• Tzeng, Sheng‐Tai
• Chang, Chia‐Yun
• Lai, Yen‐Chun
• Yen, Sou‐Jhy
• Yu, Sung‐Liang
• Yang, Ya‐Chien

Titel

Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and its genetic loss predicts adverse prognosis

Ist Teil von

• International journal of cancer, 2014-12, Vol.135 (11), p.2593-2603

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. What's new? The PCDH10 gene, which is frequently silenced by promoter hypermethylation in many carcinomas and hematological malignancies, has been reported as a novel tumor suppressor. This study reveals for the first time that genetic deletion is a contributing mechanism in PCDH10 inactivation, and that the allelic loss of PCDH10 is an independent poor prognostic marker in colorectal cancer. Ectopic expression of PCDH10 not only inhibited the behavior of tumor cells in vitro, but also restrained tumorigenesis and intrahepatic metastasis in vivo. The findings provide the new concept that loss of PCDH10 function may be involved in tumor metastasis in human cancers.