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Magnesium Absorption in Intestinal Cells: Evidence of Cross-Talk between EGF and TRPM6 and Novel Implications for Cetuximab Therapy

Risultato della ricerca: Contributo in rivistaArticolo

Abstract

Hypomagnesemia is very commonly observed in cancer patients, most frequently in association with therapy with cetuximab (CTX), a monoclonal antibody targeting the epithelial growth factor receptor (EGFR). CTX-induced hypomagnesemia has been ascribed to renal magnesium (Mg) wasting. Here, we sought to clarify whether CTX may also influence intestinal Mg absorption and if Mg supplementation may interfere with CTX activity. We used human colon carcinoma CaCo-2 cells as an in vitro model to study the mechanisms underlying Mg transport and CTX activity. Our findings demonstrate that TRPM6 is the key channel that mediates Mg influx in intestinal cells and that EGF stimulates such influx; consequently, CTX downregulates TRPM6-mediated Mg influx by interfering with EGF signaling. Moreover, we show that Mg supplementation does not modify either the CTX IC50 or CTX-dependent inhibition of ERK1/2 phosphorylation. Our results suggest that reduced Mg absorption in the intestine may contribute to the severe hypomagnesemia that occurs in CTX-treated patients, and Mg supplementation may represent a safe and effective nutritional intervention to restore Mg status without impairing the CTX efficacy.
Lingua originaleInglese
pagine (da-a)3277-N/A
RivistaNutrients
Numero di pubblicazione12
DOI
Stato di pubblicazionePubblicato - 2020

OSS delle Nazioni Unite

Questo processo contribuisce al raggiungimento dei seguenti obiettivi di sviluppo sostenibile

  1. SDG 3 - Salute e benessere
    SDG 3 Salute e benessere

All Science Journal Classification (ASJC) codes

  • Scienze Alimentari
  • Nutrizione e Dietetica

Keywords

  • EGFR
  • biomarker
  • colorectal cancer
  • hypomagnesemia
  • magnesium supplementation
  • monoclonal antibodies
  • targeted therapy

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