Psychological stress drives progression of malignant tumors via DRD2/HIF-1α signaling

Abstract

Although it is established that the sustained psychological stress conditions under which tumor patients often reside accelerates malignant progression of tumors, the molecular mechanism behind this association is unclear. In this work, the effect of psychological stress on tumor progression was verified using a stress-stimulated tumor-bearing mouse model (Str-tumor).

Both D2 dopamine receptor (DRD2) and hypoxia-inducible factor 1-alpha (HIF-1α) were highly expressed in the nucleus of stress-stimulated tumors. Treatment with trifluoperazine (TFP), a DRD2 inhibitor, elicited better antitumor effects in Str-tumors than the control group.

These results indicate that DRD2 may mediate stress-induced malignant tumor progression. DRD2 interacted with von Hippel-Lindau (VHL) in the nucleus, and competitive binding of DRD2 and HIF-1α to VHL resulted in reduced ubiquitination-mediated degradation of HIF-1α, enhancing the epithelial-mesenchymal transition (EMT) of tumor cells. TFP acted as an interface inhibitor between DRD2 and VHL to promote the degradation of HIF-1α.

In conclusion, DRD2 may promote the progression of malignant tumors induced by psychological stress via activation of the oxygen-independent HIF-1α pathway, and TFP may serve as a therapeutic strategy for stress management in cancer patients.

 

About this publication.

See also:

- Official Web Site: The Di Bella Method;

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- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

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