FCN3 functions as a tumor suppressor of lung adenocarcinoma through induction of endoplasmic reticulum stress
In this study, we report a novel function of FCN3 (Ficolin 3), a secreted lectin capable of activating the complement pathway, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of FCN3 was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and...
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Veröffentlicht in: | Cell death & disease 2021-04, Vol.12 (4), p.407-407, Article 407 |
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Sprache: | eng |
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Zusammenfassung: | In this study, we report a novel function of
FCN3
(Ficolin 3), a secreted lectin capable of activating the complement pathway, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of
FCN3
was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of
FCN3
was shown to be significantly correlated with increased mortality among LUAD patients. Interestingly, while ectopic expression of
FCN3
led to cell cycle arrest and apoptosis in A549 and H23 cells derived from LUAD, the secreted form of the protein had no effect on the cells. Rather, we found evidence indicating that activation of the unfolded protein response from endoplasmic reticulum (ER) stress is induced by ectopic expression of
FCN3
. Consistently, inhibition of ER stress response led to enhanced survival of the LUAD cells. Of note, the fibrinogen domain, which is not secreted, turned out to be both necessary and sufficient for induction of apoptosis when localized to ER, consistent with our proposed mechanism. Collectively, our data indicate that
FCN3
is a tumor suppressor gene functioning through induction of ER stress. |
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ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-021-03675-y |