2. Academic Validation
  3. E2F1-mediated ectopic expression of PP1A promotes breast cancer progression via activation of YAP1

E2F1-mediated ectopic expression of PP1A promotes breast cancer progression via activation of YAP1

  • Int J Biochem Cell Biol. 2023 Feb 12;157:106389. doi: 10.1016/j.biocel.2023.106389.
Xiaochong Deng 1,  Kaiyao Hua 1,  Amik Munankarmy 2,  Qifeng Luo 1,  Xuehui Wang 1,  Lin Fang 3
Affiliations

Affiliations

  • 1 Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
  • 2 Laboratory Medicine & Pathology, Mayo Clinic, Rochester 55902, MN, USA.
  • 3 Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. Electronic address: [email protected].
PMID: 36787863 DOI: 10.1016/j.biocel.2023.106389
Abstract

Hormone receptor-positive breast Cancer is the most common subtype of breast Cancer. The protein Phosphatase PP1A gene is described as an oncogene in several tumor types; however, the biological function of PP1A in hormone receptor-positive breast Cancer remains unclear. The Cancer Genome Atlas data indicates PP1A expression is upregulated in hormone receptor-positive breast Cancer tissues than in normal breast tissues. We explored the biological function of PP1A in hormone receptor-positive breast Cancer using MTT assays, colony formation assays, and a xenograft mouse model. The results indicated that PP1A promoted hormone receptor-positive breast Cancer proliferation, both in vitro and in vivo. Mechanistically, LINC02754 recruited the binding of the transcription factor E2F1 to the PP1A promotor, thereby increasing PP1A expression. The PP1A then interacted with and dephosphorylated YAP1, resulting in YAP1 activation. The dephosphorylated YAP1 moved to the nucleus and increased the expression of the downstream oncogene CTGF, promoting hormone receptor-positive breast Cancer progression. Our findings reveal the function of the LINC02754/E2F1/PP1A/YAP1 axis in hormone receptor-positive breast Cancer and provide new insight into hormone receptor-positive breast Cancer progression.

Keywords

E2F1; Hormone receptor-positive breast cancer; LINC02754; PP1A; YAP1.

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