Molecule Information

General Information of the Molecule (ID: Mol04382)

• Name: Cysteine-rich secretory protein 3 (CRISP3) ,Homo sapiens
• Synonyms: Specific granule protein of 28 kDa
• Molecule Type: Protein
• Gene Name: CRISP3
• Gene ID: 10321
• Sequence:
  MTLFPVLLFLVAGLLPSFPANEDKDPAFTALLTTQTQVQREIVNKHNELRRAVSPPARNM
  LKMEWNKEAAANAQKWANQCNYRHSNPKDRMTSLKCGENLYMSSASSSWSQAIQSWFDE
  Y NDFDFGVGPKTPNAVVGHYTQVVWYSSYLVGCGNAYCPNQKVLKYYYVCQYCPAGNWA
  NR LYVPYEQGAPCASCPDNCDDGLCTNGCKYEDLYSNCKSLKLTLTCKHQLVRDSCKAS
  CNC SNSIY
• Uniprot ID: CRIS3_HUMAN
• Ensembl ID: ENSG0000009600612
• HGNC ID: HGNC:16904

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

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Lobaplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Resistant Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Resistant Drug: Lobaplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: SUM159PT cells; Breast; Homo sapiens (Human); CVCL_5423/CVCL_5590
• In Vivo Model: Female nude mice model; Mus musculus
• Experiment for Molecule Alteration: qPCR; Western blot assay; Immunofluorescence staining assay; Chromatin immunoprecipitation assay
• Experiment for Drug Resistance: CCK8 cell cytotoxicity assay; Cell proliferation assay; Cell invasion assay; TUNEL analysis; Sphere-forming assay; Colony formation assay; Xenograft assay
• Mechanism Description: Here, we investigated the molecular mechanisms behind lobaplatin resistance and stemness in vitro and in vivo. Two chemoresistance-related GEO data sets (GSE70690 and GSE103115) were included to screen out relevant genes. Cysteine-rich secretory protein 3 (CRISP3) was found to be overexpressed in lobaplatin-resistant TNBC and related to poor diagnosis. CRISP3 expression was significantly correlated with tumor stemness markers in lobaplatin-resistant cells. E1A-associated protein p300 (EP300) regulated CRISP3 expression by affecting the H3K27ac modification of the CRISP3 promoter. In addition, knocking down EP300 curbed the malignant biological behavior of lobaplatin-resistant cells, which was antagonized by CRISP3 overexpression. Collectively, our results highlight the EP300/CRISP3 axis as a key driver of lobaplatin resistance in TNBC and suggest that therapeutic targeting of this axis may be an effective strategy for enhancing platinum sensitivity in TNBC.

References

• Ref 1: EP300 promotes tumor stemness via epigenetic activation of CRISP3 leading to lobaplatin resistance in triple-negative breast cancer. Hum Cell. 2024 Sep;37(5):1475-1488.