Telomerase catalyzes telomeric DNA synthesis, an essential process to maintain 
the length of telomere for continuous cell proliferation and genomic stability. 
Telomerase is activated in gametes, stem cells, and most tumor cells, and its 
activity is tightly controlled by a catalytic human telomerase reverse 
transcriptase (hTERT) subunit and a collection of associated proteins. In the 
present work, normal human testis tissue was used for the first time to identify 
proteins involved in the telomerase regulation under normal physiological 
conditions. Immunoprecipitation was performed using total protein lysates from 
the normal testis tissue and the proteins of interest were identified by 
microfluidic high-performance liquid chromatography and tandem mass spectrometry 
(HPLC-Chip-MS/MS). The regulatory role of PCDH10 in telomerase activity was 
confirmed by a telomeric repeat amplification protocol (TRAP) assay, and the 
biological functions of it were characterized by in vitro proliferation, 
migration, and invasion assays. A new in vivo hTERT interacting protein, 
protocadherin 10 (PCDH10), was identified. Overexpression of PCDH10 in 
pancreatic cancer cells impaired telomere elongation by inhibiting telomerase 
activity while having no obvious effect on hTERT expression at mRNA and protein 
levels. As a result of this critical function in telomerase regulation, PCDH10 
was found to inhibit cell proliferation, migration, and invasion, suggesting a 
tumor suppressive role of this protein. Our data suggested that PCDH10 played a 
critical role in cancer cell growth, by negatively regulating telomerase 
activity, implicating a potential value in future therapeutic development 
against cancer.