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Cancer

LPAR4 establishes a tumour-initiating niche

Nature Cell Biology volume 25, pages 217–219 (2023)Cite this article

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Tumour-initiating cells are resistant to challenging growth conditions during the initiation of pancreatic cancer, but how transformed cells acquire a stress-resistant, tumour-initiating state remains unclear. Here, the authors identify a signalling cascade in which LPAR4 induces fibronectin production, cancer stemness and a tumour-initiating niche.

Adaptation to non-optimal growth conditions such as isolation stress during tumour initiation, combined with a hypoxic and nutrient-poor tumour microenvironment, is a defining hallmark of pancreatic cancer cells. A subpopulation of tumour cells, namely tumour-initiating cells (TICs) or cancer stem cells (CSCs), possess self-renewal and stem-like features, which renders these cells fairly resistant to the challenging growth conditions during tumour initiation at both primary and metastatic sites1. Although these characteristics have been shown to be maintained by cell-intrinsic and stroma-derived factors2, whether tumour cells transiently acquire a tumour stem-cell-like phenotype in during tumour initiation remains unknown. In this issue of Nature Cell Biology, Wu et al.3 discovered a stromal-independent source of the pro-tumorigenic extracellular matrix (ECM) component fibronectin (FN1). In pancreatic cancer, the cell-autonomous production of FN1 enables tumour cells to establish their own extracellular tumour-initiating niche, before the development of the stromal reaction. The findings of Wu et al.3 highlight a signalling cascade that enables the tumour cells to switch to a more stress-resistant state and overcome the challenging growth conditions that occur during tumour initiation.

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Fig. 1: Stress-induced LPAR4 upregulation induces PDAC tumour initiation via cell-autonomous fibronectin release.

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Authors and Affiliations

  1. Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA

    Frank Arnold & Mara H. Sherman

  2. Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

    Mara H. Sherman

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  1. Frank Arnold
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  2. Mara H. Sherman
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Correspondence to Mara H. Sherman.

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Arnold, F., Sherman, M.H. LPAR4 establishes a tumour-initiating niche. Nat Cell Biol 25, 217–219 (2023). https://doi.org/10.1038/s41556-022-01038-z

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