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IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion

Rakhee Bajaj1, Samrat T Kundu2, Caitlin L Grzeskowiak3,4

  • 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.

Oncogene
|August 6, 2020
PubMed

Insights

Novel genes IMPAD1 and KDELR2 drive non-small cell lung cancer (NSCLC) invasion and metastasis by enhancing Golgi function. Inhibiting matrix metalloproteases (MMPs) reduced this cancer spread.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Metastasis Research

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
  • Cancer metastasis, the spread of cancer to distant sites, is a primary driver of NSCLC lethality.
  • Identifying molecular mechanisms and novel drivers of NSCLC invasion and metastasis is crucial for developing effective therapies.

Purpose of the Study:

  • To identify novel genetic drivers of lung cancer invasion and metastasis.
  • To elucidate the mechanism by which identified genes promote cancer cell invasion and metastasis.
  • To explore potential therapeutic strategies targeting the identified pathways.

Main Methods:

  • Conducted a gain-of-function invasion screen to identify genes promoting cancer cell invasion.
  • Utilized in vitro invasion assays and in vivo metastasis models to validate identified genes.
  • Investigated the cellular and molecular mechanisms, including ER-Golgi pathway function and secretion, associated with identified genes.
  • Assessed the efficacy of matrix metalloprotease (MMP) inhibition in suppressing gene-mediated invasion.

Main Results:

  • Identified IMPAD1 and KDELR2 as independent, robust drivers of NSCLC invasion and metastasis.
  • Demonstrated that IMPAD1 and KDELR2 enhance Golgi-mediated cellular functions and secretion.
  • Showed that therapeutic inhibition of matrix metalloproteases (MMPs) effectively suppressed invasion driven by both IMPAD1 and KDELR2.
  • Highlighted the critical role of altered Golgi function in cancer invasion and metastasis.

Conclusions:

  • IMPAD1 and KDELR2 are significant contributors to non-small cell lung cancer progression and metastasis.
  • Targeting Golgi-mediated functions and secretion represents a potential therapeutic avenue for NSCLC.
  • Matrix metalloprotease (MMP) inhibition shows promise in counteracting invasion driven by these novel oncogenes.

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