Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Upregulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath. Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1.; Osteostatin is a potent inhibitor of osteoclastic bone resorption.

1. In summary, these results reveal that PTHLH expression is a poor prognosis marker in head and neck squamous cell carcinoma patients, and RUNX2-PTHLH axis contributes to head and neck squamous cell carcinoma tumor growth. PMID: 28120940
2. Our study thus demonstrates the dual roles of PTHrP on TGF-b1 signaling and FN up-regulation for the first time in glomerular mesangial cells . These data also provided new insights to guide development of therapy for diabetic kidney disease PMID: 28954822
3. these data suggest that PTHrP(12-48) is a bioactive breast cancer-derived peptide that locally regulates the differentiation of hematopoietic cells and the activity of osteoclasts within the tumor-bone marrow microenvironment, perhaps to facilitate tumor control of bone. PMID: 28370412
4. RSK activation via ERK modulates human colon cancer cells response to PTHrP. PMID: 28385776
5. this is the first time that mutation recurrence has been detected in PTHLH associated with brachydactyly type E and we have observed that, as remarked before, this syndrome has high intrafamilial as well as interfamilial variability PMID: 28211986
6. Antagonistic antibodies against the death receptors demonstrated that Apo2L/TRAIL mediated its apoptotic signals through activation of the TRAIL-R2 in PTHrP expressing breast cancer cells PMID: 23822995
7. Amino PTHrP and carboxyl PTHrP can vary independently in different lung carcinomas. Carboxyl PTHrP may temper the stimulatory effect of amino PTHrP on cancer progression. PMID: 28342003
8. PTHLH is a gastrin-regulated growth factor that might contribute to gastric epithelial cell homeostasis. PMID: 28408643
9. Duplication of PTHLH co-segregates with osteochondroplasia with a combined brachydactyly type E/A1 in a three-generation pedigree. PMID: 26733284
10. Data shown here expand the knowledge on the phenotypic presentation of PTHLH mutations, highlighting significant clinical variability and incomplete penetrance of the PTHLH-related symptoms. PMID: 26763883
11. We showed that the supplementation of the osteogenic differentiation medium with PTHrP inhibited the alkaline phosphatase activity and the expression of the transcription factor DLX3, but the depletion of PTHrP did not support the differentiation of DFCs.We showed that SUFU (Suppressor Of Fused Homolog) was not regulated during the osteogenic differentiation in DFCs PMID: 27368119
12. High expression of PTHRP is associated with Tongue squamous cell carcinoma. PMID: 27316348
13. No relationship between plasma PTHrP levels and failure of tooth eruption, dental manifestations of pseudohypoparathyroidism or brachydactyly was found. PMID: 26855372
14. we report three patients affected with brachydactyly type E, caused by PTHLH mutations expected to result in haploinsufficiency, and discuss our data compared to published reports. PMID: 26640227
15. TGF-beta and PTHrP were confirmed to be involved in regulating the malignant progression in breast cancer, and PTHrP expression, to be associated with bone metastasis as a potential prognostic marker in ER negative breast cancer PMID: 26597083
16. Data suggest affinity of ligands for binding site on PTH1R/parathyroid hormone 1 receptor, either in GTP-binding protein-dependent or -independent conformation, alters duration of action of ligand in target cells; ligands were peptide fragments of PTHRP. PMID: 26562265
17. A novel heterozygous mutation in PTHLH gene was identified in a Chinese pedigree with brachydactyly type E. PMID: 25801215
18. PTHLH/PTHrP could play a role in the pathogenesis of oral squamous cell carcinoma by affecting cell proliferation and cell cycle. PMID: 25539663
19. PTHrP regulates Caco-2 cell proliferation via several signaling pathways. PMID: 25053227
20. Intermittent application of PTHrP represents an important novel means to improve chondrogenesis of MSCs and may be considered as a supporting clinical-treatment mode for MSC-based cartilage defect regeneration PMID: 24836507
21. Data show three individuals with duplications of the parathyroid hormone-like hormone (PTHLH) locus leading to a hitherto unrecognized syndrome characterized by acro-osteolysis, cortical irregularity of long bones and metadiaphyseal enchondromata. PMID: 25007883
22. PTHrP positively modulates cell cycle progression and changes the expression of proteins involved in cell cycle regulation. PMID: 25051885
23. miR-126-5p could directly target PTHrP and have a tumor suppressor function in giant cell tumor. PMID: 24973691
24. High PTHLH expression is strongly associated with poor outcome both in overall survival and disease-free survival for patients who underwent standard nephrectomy. PMID: 24861371
25. High PTHRP expression is associated with bone destruction in lung and breast cancer. PMID: 25359619
26. Threonine at position 107 contributes to the osteogenic actions of PTHrP in osteoblasts. PMID: 24725082
27. High PTHRP expression is associated with metastasis in breast cancer. PMID: 25368276
28. PTHLH is important during embryonic development. [review] PMID: 25252304
29. Data suggest that parathyroid hormone-related protein (PTHrP) may work through epithelial-to-mesenchymal transition (EMT) to promote an aggressive and metastatic phenotype in prostate cancer. PMID: 24465715
30. PTHrP mediates energy wasting in fat tissues and contributes to the broader aspects of cancer cachexia; thus, neutralization of PTHrP might hold promise for ameliorating cancer cachexia and improving patient survival PMID: 25043053
31. It is a critical physiological regulator of various biological processes, including bone and cartilage metabolism. (review) PMID: 24870837
32. PTHrP was found to inhibit DKK1 expression through c-Jun-mediated inhibition of beta-catenin activity on the DKK1 promoter. PMID: 23752183
33. Evaluation of clinical breast tumor samples revealed that reduced DLC1 expression was linked to elevated PTHLH expression and organ-specific metastasis to bone. PMID: 24590291
34. High PTHRP mRNA expression correlated with lung cancer stage, presence of bone metastasis, and squamous cell carcinoma. PMID: 23810363
35. PTHrP expression in human MDA-MB-231 breast cancer cells is critical for tumor growth and survival and osteoblast inhibition. PMID: 23983616
36. PTHrP intracellular retention is down-regulated in osteo-differentiating cells whereas the secretion of the protein in the extracellular medium is up-regulated with respect to stem cells. PMID: 23810909
37. these results evidence a protective effect of PTHrP under apoptotic conditions in intestinal cells. PMID: 23845990
38. Data indicate that expressions of PTHrP, EPO, and VEGF were respectively related to advanced stage of clear cell renal cell carcinoma (ccRCC). PMID: 23780896
39. Prostate cancer-derived PTHrP acts in the bone marrow to potentiate CD11b(+)Gr1(+) cells, which are recruited to tumor tissue where they contribute to tumor angiogenesis and growth. PMID: 24072746
40. PTHrP excreted by giant cell tumor of bone stromal cells increases bone tumor cell local invasiveness and migration. PMID: 23466453
41. new clues to understand the underlying mechanisms whereby PTHrP can increase bone formation. PMID: 23494914
42. PTHrP is highly detectable in intermediate and epidermoid cells, and abundant expression of PTHrP in intermediate cells has a significant association with cancer malignancy. PMID: 23588777
43. All 3 markers were studied independently and were associated with tumor percentage in metastatic lymph nodes. PVA had the strongest correlation, followed by PTHrP and then TACSTD1. PMID: 23625795
44. Parathyroid hormone-related protein is induced by hypoxia and promotes expression of the differentiated phenotype of human articular chondrocytes. PMID: 23662774
45. findings represent the initial genetic evidence that PTHrP regulates periosteal/intramembranous bone cell activity on cortical bone surfaces and indicate that PTHrP serves as a load-induced modeling tool in fibrous insertion sites during linear growth PMID: 23109045
46. that miR-33a may be a potent tumor suppressor, which inhibits direct and indirect osteoclastogenesis through repression of PTHrP. PMID: 23458685
47. PTHrP increases the promoter activity of the integrin alpha6 and beta4 subunits. PMID: 23499737
48. Tristetraproline (TTP) is an RNA-binding protein that may be involved in ARE-mediated degradation of parathyroid hormone-related protein. PMID: 22960231
49. activated PTHLH coupling feedback phosphoinositide to G-protein receptor signal-induced cell adhesion network in hepatocellular carcinoma PMID: 22997493
50. systems theory analysis of PTHLH downstream leukocyte adhesion-mediated protein amino acid N-linked glycosylation coupling Notch and JAK-STAT cascade to iron-sulfur cluster assembly-induced aging network in no-tumor hepatitis/cirrhotic tissues PMID: 22955522

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Cytoplasm. Nucleus. Secreted.

Parathyroid hormone family

Ubiquitous. Also expressed in the mammary gland.

HGNC: 9607

OMIM: 168470

KEGG: hsa:5744

STRING: 9606.ENSP00000379213

UniGene: Hs.591159