Mammary gland development pathway - Involution (Stage 4 of 4) (Homo sapiens)

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213132133MAMMARY GLAND DEVELOPMENTPATHWAYPregnancy and lactationSOCS3-STAT3 signaling pathwaySTAT3CHI3L1CDH1STAT5TP53E2F1MYCIL6STBAXMMP9SOCS3DNAEmbryonic developmentPubertyInvolutionDNA


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.

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Ontology Terms



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


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102408view19:59, 22 December 2018EgonwReplaced a secondary ChEBI ID with primary ID.
102399view14:19, 22 December 2018DeSlAdded STAT5 Interpro family ID
88702view16:18, 12 August 2016JmeliusOntology Term : 'regulatory pathway' added !
78062view19:44, 24 November 2014MaintBotSwitched vertical lines from interactions to graphical lines
78061view19:35, 24 November 2014MaintBotAdded data node xrefs
77102view22:05, 17 July 2014KhanspersOntology Term : 'milk secreting cell' added !
75431view19:29, 29 May 2014Biodados
75430view19:20, 29 May 2014BiodadosModified description
75429view19:09, 29 May 2014BiodadosNew pathway

External references


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NameTypeDatabase referenceComment
BAXGeneProduct581 (Entrez Gene)
CDH1GeneProduct999 (Entrez Gene)
CHI3L1GeneProduct1116 (Entrez Gene)
DNAMetaboliteCHEBI:16991 (ChEBI)
E2F1GeneProduct1869 (Entrez Gene)
IL6STGeneProduct3572 (Entrez Gene)
MMP9GeneProduct4318 (Entrez Gene)
MYCGeneProduct4609 (Entrez Gene)
SOCS3GeneProduct9021 (Entrez Gene)
STAT3GeneProduct6774 (Entrez Gene)
STAT5GeneProductIPR035858 (InterPro)
TP53GeneProduct7157 (Entrez Gene)

Annotated Interactions

No annotated interactions

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