Mammary gland development pathway - Involution (Stage 4 of 4) (WP2815)

Homo sapiens

After pregnancy and lactation, the mammary gland undergoes a tissue remodeling process, known as involution. This process is characterized by the alveoli degeneration through apoptosis. CHI3L1 inhibits mammary epithelial cell differentiation and polarization in the presence of lactogenic hormones, such as prolactin, hydrocortisone and insulin. CHI3L1 suppress CDH1 and increases MMP9 and this is an important process for involution [ 1]. In the SOCS3-STAT3 signaling pathway, STAT5 induces SOCS3, which binds to its receptor, IL6ST. Then, IL6ST activates STAT3 [ 2]. SOCS3/STAT3 signaling pathway is associated with MYC and, thereafter, with MYC target genes such as TP53, BAX and E2F1. Changes in the SOCS3/STAT3 signaling pathway affect MYC. As SOCS3 has an anti-apoptotic function and MYC an apoptotic function, SOCS3 is considered an important regulator of involution [ 3].


Lab. Biodados UFMG , Kristina Hanspers , Jonathan Mélius , Denise Slenter , Egon Willighagen , and Eric Weitz


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Homo sapiens



Cell Type Ontology

milk secreting cell

Pathway Ontology

regulatory pathway


Label Type Compact URI Comment
DNA Metabolite chebi:16991
DNA Metabolite chebi:16991
CHI3L1 GeneProduct ncbigene:1116
STAT5 GeneProduct interpro:IPR035858
SOCS3 GeneProduct ncbigene:9021
MYC GeneProduct ncbigene:4609
MMP9 GeneProduct ncbigene:4318
E2F1 GeneProduct ncbigene:1869
STAT3 GeneProduct ncbigene:6774
TP53 GeneProduct ncbigene:7157
BAX GeneProduct ncbigene:581
CDH1 GeneProduct ncbigene:999
IL6ST GeneProduct ncbigene:3572


  1. Information networks in the mammary gland. Hennighausen L, Robinson GW. Nat Rev Mol Cell Biol. 2005 Sep;6(9):715–25. PubMed Europe PMC Scholia
  2. Knocking off SOCS genes in the mammary gland. Sutherland KD, Lindeman GJ, Visvader JE. Cell Cycle. 2007 Apr 1;6(7):799–803. PubMed Europe PMC Scholia
  3. Inhibitory activity of YKL-40 in mammary epithelial cell differentiation and polarization induced by lactogenic hormones: a role in mammary tissue involution. Scully S, Yan W, Bentley B, Cao QJ, Shao R. PLoS One. 2011;6(10):e25819. PubMed Europe PMC Scholia