Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation

Wei Min Chang, Yuan Feng Lin, Chia Yi Su, Hsuan Yu Peng, Yu Chan Chang, Jenn Ren Hsiao, Chi Long Chen, Jang Yang Chang, Yi Shing Shieh, Michael Hsiao, Shine Gwo Shiah

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Abstract

Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth. In patients, PTHLH is a poor prognosis marker. PTHLH expression lead to increasing the cell proliferation potential through an autocrine/paracrine role and elevating blood calcium level in Nod-SCID mice. In public HNSCC microarray cohorts, PTHLH is found to be co-expressed with RUNX2. Physiologically, PTHLH is regulated by RUNX2 and also acting as key calcium regulator. However, elevations of calcium concentration also increased the RUNX2 expression. PTHLH, calcium, and RUNX2 form a positive feedback loop in HNSCC. Furthermore, ectopic RUNX2 expression also increased PTHLH expression and promoted proliferation potential through PTHLH expression. Using cDNA microarray analysis, we found PTHLH also stimulated expression of cell cycle regulators, namely CCNA2, CCNE2, and CDC25A in HNSCC cells, and these genes are also up-regulated in HNSCC patients. In summary, our results reveal that PTHLH expression is a poor prognosis marker in HNSCC patients, and RUNX2-PTHLH axis contributes to HNSCC tumor growth.

Original languageEnglish
Article number41131
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Jan 25 2017

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Head and Neck Neoplasms
Parathyroid Hormone
Hormones
Growth
Calcium
Carcinoma, squamous cell of head and neck
SCID Mice
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Cell Cycle
Cell Proliferation
Ligands

ASJC Scopus subject areas

  • General

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Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation. / Chang, Wei Min; Lin, Yuan Feng; Su, Chia Yi; Peng, Hsuan Yu; Chang, Yu Chan; Hsiao, Jenn Ren; Chen, Chi Long; Chang, Jang Yang; Shieh, Yi Shing; Hsiao, Michael; Shiah, Shine Gwo.

In: Scientific Reports, Vol. 7, 41131, 25.01.2017.

Research output: Contribution to journalArticle

Chang, Wei Min ; Lin, Yuan Feng ; Su, Chia Yi ; Peng, Hsuan Yu ; Chang, Yu Chan ; Hsiao, Jenn Ren ; Chen, Chi Long ; Chang, Jang Yang ; Shieh, Yi Shing ; Hsiao, Michael ; Shiah, Shine Gwo. / Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation. In: Scientific Reports. 2017 ; Vol. 7.
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abstract = "Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth. In patients, PTHLH is a poor prognosis marker. PTHLH expression lead to increasing the cell proliferation potential through an autocrine/paracrine role and elevating blood calcium level in Nod-SCID mice. In public HNSCC microarray cohorts, PTHLH is found to be co-expressed with RUNX2. Physiologically, PTHLH is regulated by RUNX2 and also acting as key calcium regulator. However, elevations of calcium concentration also increased the RUNX2 expression. PTHLH, calcium, and RUNX2 form a positive feedback loop in HNSCC. Furthermore, ectopic RUNX2 expression also increased PTHLH expression and promoted proliferation potential through PTHLH expression. Using cDNA microarray analysis, we found PTHLH also stimulated expression of cell cycle regulators, namely CCNA2, CCNE2, and CDC25A in HNSCC cells, and these genes are also up-regulated in HNSCC patients. In summary, our results reveal that PTHLH expression is a poor prognosis marker in HNSCC patients, and RUNX2-PTHLH axis contributes to HNSCC tumor growth.",
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AU - Chang, Yu Chan

AU - Hsiao, Jenn Ren

AU - Chen, Chi Long

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