STAT3 and MCL-1 associate to cause a mesenchymal epithelial transition.
Embryo implantation is effected by a myriad of signaling cascades acting on the embryo-endometrium axis. Here we show, by using MALDI TOF analysis, far-western analysis and colocalization and co-transfection studies, that STAT3 and MCL-1 are interacting partners during embryo implantation. We show in vitro that the interaction between the two endogenous proteins is strongly regulated by estrogen and progesterone. Implantation, pregnancy and embryogenesis are distinct from any other process in the body, with extensive, but controlled, proliferation, cell migration, apoptosis, cell invasion and differentiation. Cellular plasticity is vital during the early stages of development for morphogenesis and organ homeostasis, effecting the epithelial to mesenchymal transition (EMT) and, the reverse process, mesenchymal to epithelial transition (MET). STAT3 functionally associates with MCL-1 in the mammalian breast cancer cell line MCF7 that overexpresses STAT3 and MCL-1, which leads to an increased rate of apoptosis and decreased cellular invasion, disrupting the EMT. Association of MCL-1 with STAT3 modulates the normal, anti-apoptotic, activity of MCL-1, resulting in pro-apoptotic effects. Studying the impact of the association of STAT3 with MCL-1 on MET could lead to an enhanced understanding of pregnancy and infertility, and also metastatic tumors.
Utero-Embryo Repromics Lab, Division of Molecular Reproduction, Rajiv Gandhi Centre for Biotechnology, Thycaud PO, Poojappura, Thiruvananthapuram 695 014, Kerala, India.
A P
AP
Renjini
Shiny
S
Titus
Prashanth
P
Narayan
Megha
M
Murali
Rajesh Kumar
RK
Jha
Malini
M
Laloraya
D000818:Animals; D017209:Apoptosis; D054338:Cell Transdifferentiation; D010064:Embryo Implantation; D004967:Estrogens / Q000502:physiology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021381:Protein Transport; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D014599:Uterus / Q000166:cytology / Q000378:metabolism
D004967:Estrogens; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D011374:Progesterone
Apoptosis; Epithelial mesenchymal transition; Invasion; MET; STAT3–MCL-1 interaction