Fig. 1
From: Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer
Crosstalk between PRLR and EGFR/HER2 signaling to promote breast cancer progression. PRL endorses PRLR activation, which recruits downstream pathways, such as JAK/STAT, MAPK/ERK, PI3K/AKT/mTOR, NEK3/VAV2/RhoA and TEC/VAV1/RAC1 involved in growth, survival, and migration of breast cancer. EGF/EGFR signaling somewhat overlaps with PRLR signaling to result in the activation of similar downstream events. PRLR/HER2 crosstalk endorses ER phosphorylation and promotes its attachment to the PRLR regulator and promotes PRLR transcription. EGF/EGFR can also trigger PRLR transcription in MAPK/PI3K-dependent manner. In addition, PRL/PRLR activation recruits HRE2 via JAK2 resulting an activation of FAC signaling that promotes cell adherence and induces metastasis. Arrows represent downstream events. AKT, Ak strain transforming; EGF, Epidermal growth factor; EGFR, Epidermal growth factor receptor; ER, Estrogen receptor; ERK, Extracellular signal-regulated kinase; GRB2, Growth factor receptor-bound protein 2; HER2, Human epidermal growth factor-2; JAK, Janus kinase, MAPK, Mitogen-activated protein kinase; mTOR, Mammalian target of rapamycin; NEK3, NIMA-related kinase 3; P, Phosphate; PI3K, Phosphoinositide 3-kinase; PRL, Prolactin; PRLR: Prolactin receptor; RhoA, Ras homolog family member A; STAT, Signal transducer and activator of transcription; TEK, TEK receptor tyrosine kinase; VAV, Vav guanine nucleotide exchange factor 1