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Comment
. 2023 Feb 16;388(7):657-659.
doi: 10.1056/NEJMcibr2213497.

Uncoupling Metastasis from Tumorigenesis

Karuna Ganesh  1
Affiliations
Comment

Uncoupling Metastasis from Tumorigenesis

Karuna Ganesh. N Engl J Med. .
No abstract available

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Figures

Figure 1.
Figure 1.. Dissemination of Tumor and Nontransformed Epithelial Cells.
In a recent study, Rahrmann et al. investigated the effects of deleting or inhibiting the function of the sodium leak channel nonselective protein (NALCN) in tumors and nontransformed epithelia. Using mouse models of gastric, intestinal, and pancreatic cancer harboring oncogenic Kras and Tp53 alleles, they found that organspecific NALCN deletion did not affect tumor initiation or primary tumor growth but increased tumor cell shedding into the circulation, circulating tumor-cell numbers, and metastases in multiple organs. When NALCN was deleted in the same organs in mice without any oncogenic mutations, no tumors formed, but increased numbers of NALCN-deficient cells were detected both in the circulation and in newly established cell colonies in distant organs of older mice, which showed evidence of fibrosis. NALCN-deleted fluorescent circulating nontumor cells that were injected into immunosuppressed recipient mice trafficked into organ parenchyma and generated morphologically normal structures, including renal glomeruli and tubules.
See this image and copyright information in PMC

Comment on

  • The NALCN channel regulates metastasis and nonmalignant cell dissemination.
    Rahrmann EP, Shorthouse D, Jassim A, Hu LP, Ortiz M, Mahler-Araujo B, Vogel P, Paez-Ribes M, Fatemi A, Hannon GJ, Iyer R, Blundon JA, Lourenço FC, Kay J, Nazarian RM, Hall BA, Zakharenko SS, Winton DJ, Zhu L, Gilbertson RJ. Rahrmann EP, et al. Nat Genet. 2022 Dec;54(12):1827-1838. doi: 10.1038/s41588-022-01182-0. Epub 2022 Sep 29. Nat Genet. 2022. PMID: 36175792 Free PMC article.

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