Loss of RPTPγ primes breast tissue for acid extrusion, promotes malignant transformation and results in early tumour recurrence and shortened survival

Autor:	Rasmus A, Sloth, Trine V, Axelsen, Maria Sofia, Espejo, Nicolai J, Toft, Ninna C S, Voss, Mark, Burton, Mads, Thomassen, Pernille, Vahl, Ebbe, Boedtkjer
Rok vydání:	2022
Předmět:	Mice Knockout Mice Cell Transformation Neoplastic Receptor-Like Protein Tyrosine Phosphatases Class 5 Tumor Microenvironment Animals Humans Breast Neoplasms Female Hydrogen-Ion Concentration Neoplasm Recurrence Local
Zdroj:	British journal of cancer. 127(7)
ISSN:	1532-1827
Popis:	While cellular metabolism and acidic waste handling accelerate during breast carcinogenesis, temporal patterns of acid-base regulation and underlying molecular mechanisms responding to the tumour microenvironment remain unclear.We explore data from human cohorts and experimentally investigate transgenic mice to evaluate the putative extracellular HCORPTPγ expression declines during human breast carcinogenesis and particularly in high-malignancy grade breast cancer. Low RPTPγ expression associates with poor prognosis in women with Luminal A or Basal-like breast cancer. RPTPγ knockout in mice favours premalignant changes in macroscopically normal breast tissue, accelerates primary breast cancer development, promotes malignant breast cancer histopathologies, and shortens recurrence-free survival. In RPTPγ knockout mice, expression of NaLoss of RPTPγ accelerates cellular net acid extrusion and elevates NBCn1 expression in breast tissue. As these effects precede neoplastic manifestations in histopathology, we propose that RPTPγ-dependent enhancement of Na
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::bd379897825efa11a32b6a5cb8065f9d https://pubmed.ncbi.nlm.nih.gov/35821297 Zobrazit plný text záznamu Full text from SpringerLink