Molecule Information

General Information of the Molecule (ID: Mol01937)

• Name: Geranylgeranyl diphosphate synthase 1 (GGPS1) ,Homo sapiens
• Synonyms: GGPS1
• Molecule Type: Protein
• Gene Name: GGPS1
• Gene ID: 9453
• Location: chr1:235,327,350-235,344,532[+]
• Sequence:
  MEKTQETVQRILLEPYKYLLQLPGKQVRTKLSQAFNHWLKVPEDKLQIIIEVTEMLHNAS
  LLIDDIEDNSKLRRGFPVAHSIYGIPSVINSANYVYFLGLEKVLTLDHPDAVKLFTRQLL
  ELHQGQGLDIYWRDNYTCPTEEEYKAMVLQKTGGLFGLAVGLMQLFSDYKEDLKPLLNTL
  GLFFQIRDDYANLHSKEYSENKSFCEDLTEGKFSFPTIHAIWSRPESTQVQNILRQRTEN
  IDIKKYCVHYLEDVGSFEYTRNTLKELEAKAYKQIDARGGNPELVALVKHLSKMFKEENE
• 3D-structure: PDB ID: 2Q80; Classification: Transferase; Method: X-ray diffraction; Resolution: 2.70 Å
• Function: Catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.
• Uniprot ID: GGPPS_HUMAN
• Ensembl ID: ENSG00000152904
• HGNC ID: HGNC:4249

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Small cell lung carcinoma [ICD-11: 2C25.1] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Small cell lung carcinoma [ICD-11: 2C25.1]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Small cell lung carcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.06E-02; Fold-change: 8.03E-02; Z-score: 2.18E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Biosynthesis of terpenoids and steroids; Activation; hsa01062
• Cell Pathway Regulation: Indole diterpene alkaloid biosynthesis; Activation; hsa00403
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: H146 cells; Lung; Homo sapiens (Human); CVCL_1473
• In Vitro Model: H209 cells; Lung; Homo sapiens (Human); CVCL_9V41
• In Vitro Model: H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: H526 cells; Lung; Homo sapiens (Human); CVCL_1569
• In Vitro Model: H82 cells; Lung; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase?1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Small cell lung carcinoma [ICD-11: 2C25.1] [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Small cell lung carcinoma [ICD-11: 2C25.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.06E-20; Fold-change: 4.40E-02; Z-score: 9.57E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Biosynthesis of terpenoids and steroids; Activation; hsa01062
• Cell Pathway Regulation: Indole diterpene alkaloid biosynthesis; Activation; hsa00403
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: H146 cells; Lung; Homo sapiens (Human); CVCL_1473
• In Vitro Model: H209 cells; Lung; Homo sapiens (Human); CVCL_9V41
• In Vitro Model: H446 cells; Lung; Homo sapiens (Human); CVCL_1562
• In Vitro Model: H526 cells; Lung; Homo sapiens (Human); CVCL_1569
• In Vitro Model: H82 cells; Lung; Homo sapiens (Human); CVCL_1591
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Mechanistically, statins induce oxidative stress accumulation and apoptosis through the GGPP synthase?1 (GGPS1)-RAB7A-autophagy axis. Statin treatment overcomes both intrinsic and acquired SCLC chemoresistance in vivo across different SCLC PDX models bearing high GGPS1 levels. Moreover, we show that GGPS1 expression is negatively associated with survival in patients with SCLC

Fluvastatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [ICD-11: 2C60.3] [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Fluvastatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Breast cancer [ICD-11: 2C60]
• The Specified Disease: Breast cancer
• The Studied Tissue: Breast tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.77E-55; Fold-change: 1.07E-01; Z-score: 1.81E+01
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Steroid biosynthesis signaling pathway; Activation; hsa00100
• Cell Pathway Regulation: Terpenoid bacKbone biosynthesis signaling pathway; Activation; hsa00900
• Cell Pathway Regulation: Steroid hormone biosynthesis signaling pathway; Activation; hsa00140
• In Vitro Model: MCF-10A-neoT cells; Breast; Homo sapiens (Human); CVCL_5554
• In Vivo Model: SV40 C3TAg transgenic mouse model; Mus musculus
• Experiment for Molecule Alteration: Clariom D RNA profiling assay
• Experiment for Drug Resistance: MTT assay; Colony formation assay
• Mechanism Description: Acquired resistance to fluvastatin is mediated by restorative upregulation of cholesterol biosynthesis pathway genes.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.77E-55; Fold-change: 5.78E-01; Z-score: 1.12E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.14E-12; Fold-change: 6.97E-01; Z-score: 1.36E+00

References

• Ref 1: Ceramide kinase confers tamoxifen resistance in estrogen receptor-positive breast cancer by altering sphingolipid metabolism. Pharmacol Res. 2023 Jan;187:106558.
• Ref 2: Gene signature associated with resistance to fluvastatin chemoprevention for breast cancer .BMC Cancer. 2022 Mar 17;22(1):282. doi: 10.1186/s12885-022-09353-2. 10.1186/s12885-022-09353-2