Particulate matter facilitates amphiregulin-dependent lung cancer proliferation through glutamine metabolism

Int J Biol Sci. 2024 May 27;20(8):3126-3139. doi: 10.7150/ijbs.96210. eCollection 2024.

Abstract

Although many cohort studies have reported that long-term exposure to particulate matter (PM) causes lung cancer, the molecular mechanisms underlying the PM-induced increases in lung cancer progression remain unclear. We applied the lung cancer cell line A549 (Parental; A549.Par) to PM for an extended period to establish a mimic PM-exposed lung cancer cell line, A549.PM. Our results indicate that A549.PM exhibits higher cell growth and proliferation abilities compared to A549.Par cells in vitro and in vivo. The RNA sequencing analysis found amphiregulin (AREG) plays a critical role in PM-induced cell proliferation. We observed that PM increases AREG-dependent lung cancer proliferation through glutamine metabolism. In addition, the EGFR/PI3K/AKT/mTOR signaling pathway is involved in PM-induced solute carrier family A1 member 5 (SLC1A5) expression and glutamine metabolism. Our findings offer important insights into how lung cancer proliferation develops upon exposure to PM.

Keywords: Amphiregulin; Glutamine metabolism; Lung cancer; Particulate matter; SLC1A5.

MeSH terms

  • A549 Cells
  • Amino Acid Transport System ASC / genetics
  • Amino Acid Transport System ASC / metabolism
  • Amphiregulin* / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Glutamine* / metabolism
  • Humans
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • Minor Histocompatibility Antigens
  • Particulate Matter* / adverse effects
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Amino Acid Transport System ASC
  • Amphiregulin
  • AREG protein, human
  • Glutamine
  • Minor Histocompatibility Antigens
  • Particulate Matter
  • SLC1A5 protein, human
  • TOR Serine-Threonine Kinases