{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T16:19:27Z","timestamp":1755793167043,"version":"3.44.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The human liver-related putative tumor suppressor LPTS\/PinX1 is a gene encoding a telomerase inhibitory protein. Overexpression of LPTS\/PinX1 protein can inhibit the growth of multiple telomerase-positive cancer cell lines. LPTS\/PinX1 has therapeutic potential for cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We statistically analyzed the level of LPTS\/PinX1 protein in 9 cancer cell lines. LPTS\/PinX1158-328 (exon 7 of LPTS) was fused with TAT to generate the recombinant protein TPCH. The effects of the TPCH protein on cell growth, senescence and apoptosis in 14 cell lines were analyzed <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The purified TPCH protein was delivered into cells and inhibited telomerase activity. Also it inhibited the growth of 11 telomerase-positive cancer cell lines, was ineffective in 3 telomerase-negative cell lines <jats:italic>in vitro<\/jats:italic> and inhibited the growth of MCF-7, A549 and SW480 cell line-derived xenograft (CDX) and liver cancer patient-derived xenograft (PDX) mouse models <jats:italic>in vivo.<\/jats:italic> The inhibitory effect on the cancer cell growth was negatively correlated with the telomere length. The TPCH protein induced senescence and apoptosis in telomerase-positive cancer cells through the p21 signaling pathway and inhibited the migration of telomerase-positive cancer cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The TPCH protein strongly inhibited telomerase activity and suppressed the growth of all tested human telomerase-positive cancer cell lines <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Therefore, it could be developed as a broad-spectrum anticancer agent with low toxicity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1643155","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T04:10:44Z","timestamp":1755231044000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein 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