|
| Study | Year | Type of cancer | Contribution |
|
| Snell et al. [16–20] | 1984–1988 | Hepatoma (rat) | (i) Elevation of PHGDH |
| (ii) Did not respond to changes in dietary protein level |
| (iii) Correlated with increased rate of serine biosynthesis |
| (iv) Correlated with tumorigenic rate of growth |
| (v) Associated with neoplastic transformation and progression |
| (vi) Corresponding increases in serine hydroxymethyltransferase activity, absence of serine dehydratase and serine aminotransferase (Figure 2) |
| Sarcoma (rat) | (i) Consistent effects |
| Colon carcinoma (human) | (i) Consistent effects |
|
|
Cho et al. [22] | 2000 | Leukemia (human) | (i) Detectable 2.1 kb and 710 bp mRNA PHGDH transcripts |
| T-cell lymphoblastic lymphoma (human) | (i) Detectable 2.1 kb and 710 bp mRNA PHGDH transcripts |
| Colon adenocarcinoma (human) | (i) Detectable 2.1 kb and 710 bp mRNA PHGDH transcripts |
| Epithelioid carcinoma (human) | (i) Detectable 2.1 kb and 710 bp mRNA PHGDH transcripts |
| Lymphoma (murine) | (i) Detectable 2.1 kb and 710 bp mRNA PHGDH transcripts |
|
|
Pollari et al. [23] | 2011 | Bone metastatic breast cancer | (i) Enhanced serine production |
| (ii) Stimulation of osteoclastogenesis |
| (iii) Genetic upregulation of PHGDH, PSAT1, and PSPH (Figure 2) |
| (iv) Association with shorter time to relapse, reduced survival time, and several “clinically relevant features” |
|
|
Possemato et al. [21] |
2011 |
Breast cancer | (i) PHGDH gene exists in a region of chromosome 1p (1p12) amplified in several types of cancer |
| (ii) Elevated protein expression in estrogen receptor-negative breast cancer, relative to estrogen receptor-positive tumors approx. 68% mRNA and 70% protein elevations |
| (iii) Protein levels were elevated in estrogen receptor-negative cells lacking genetic copy number gains |
| (iv) Drives glucose-originating flux through the biosynthetic serine pathway |
| (v) Serine production is not the only important role for PHGDH in cancer cells → parallel increase in PSAT1 expression and conversion of glutamate to aKG |
|
|
Locasale et al. [8] |
2011 | Melanoma | (i) “Substantial fraction” of glycolytic flux diverted to serine production |
| (ii) PHGDH gene exists in a region of chromosome 1p (1p12) amplified in several types of cancer |
| (iii) Found localized amplification of PHGDH within the coding region of the gene |
| (iv) Elevated protein expression in human melanoma cells |
| Breast cancer | (i) High protein expression associated with triple-negative and basal subtypes but did not associate with metastasis or tumor size (contrary to previous results) |
|
|
Liu et al. [24] |
2013 |
Astrocytoma/glioma | (i) Elevation in brain tissue not normally expressing PHGDH |
| (ii) Correlated with progressively advanced tumor grade |
| (iii) Stabilizing binding interaction with oncogenic transcription factor FOXM1, induction of a series of known oncogenes |
|
|
Jing et al. [25] | 2013 | Cervical cancer | (i) Elevated protein expression in squamous cell carcinoma |
| (ii) Associated with tumor progression, stage, and size |
|
|
Noh et al. [26] |
2014 |
Triple-negative breast cancer | (i) Basal marker-positive patients exhibited increased protein expression relative to basal marker-negative patients |
| (ii) Protein expression was high in patients with mixed basal-like subtypes; 89.3% of mixed subtypes showed partial expression of basal markers |
|
