Mammalian sterile-like 1 kinase inhibits TGFβ and EGF‑dependent regulation of invasiveness, migration and proliferation of HEC-1-A endometrial cancer cells.
Transforming growth factor-β (TGFβ) and epidermal growth factor (EGF) are two potent regulators of tumorigenesis. Signaling cross-talk of TGFβ and EGF employs a number of regulators which define the impact on cell physiology. MST1 has recently been reported as a regulator of tumorigenesis and differentiation. To investigate the role of mammalian sterile-like 1 (MST1) in TGFβ and EGF signaling, we established transiently MST1‑transfected HEC-1-A endometrial cancer cells, and subjected the cells to treatment with TGFβ1, EGF and their combination. We report MST1 as a negative regulator of combined TGFβ and EGF signaling. We observed that enhanced expression of MST1 inhibited the combined action of TGFβ1 and EGF on cell invasiveness, migration and proliferation. Monitoring of the intracellular regulatory proteins showed that MST1 contribution to the TGFβ-EGF cross-talk may involve focal adhesion kinase and E-cadherin, but not activation of Smad2. Our data unveiled the role of MST1 as a negative feedback for TGFβ1‑ and EGF‑regulated cell invasiveness, migration and proliferation.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SE-17176, Sweden.
Sanaz
S
Attarha
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SE-17176, Sweden.
Sonia
S
Andersson
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, SE-17176, Sweden.
Miriam
M
Mints
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SE-17176, Sweden.
Serhiy
S
Souchelnytskyi
D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009361:Neoplasm Invasiveness / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000502:physiology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C082332:macrophage stimulating protein; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor