Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness

Cell Death & Disease
Shu-Huei ChoYi-Ching Wang

Abstract

Recent studies have revealed that dysregulated Rab small GTPase-mediated vesicle trafficking pathways are associated with cancer progression. However, whether any of the Rabs plays a suppressor role in cancer stemness is least explored. Rab37 has been postulated as a tumor suppressive small GTPase for trafficking anti-tumor cargos. Here, we report a previously uncharacterized mechanism by which Rab37 mediates exocytosis of secreted frizzled-related protein-1 (SFRP1), an extracellular antagonist of Wnt, to suppress Wnt signaling and cancer stemness in vitro and in vivo. Reconstitution experiments indicate that SFRP1 secretion is crucial for Rab37-mediated cancer stemness suppression and treatment with SRPP1 recombinant protein reduces xenograft tumor initiation ability. Clinical results confirm that concordantly low Rab37, low SFRP1, and high Oct4 stemness protein expression profile can be used as a biomarker to predict poor prognosis in lung cancer patients. Our findings reveal that Rab37-mediated SFRP1 secretion suppresses cancer stemness, and dysregulated Rab37-SFRP1 pathway confers cancer stemness via the activation of Wnt signaling. Rab37-SFRP1-Wnt axis could be a potential therapeutic target for attenuating lung cancer ste...Continue Reading

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Citations

Feb 26, 2021·Communicative & Integrative Biology·Cheng-I Jonathan Ma, Julie A Brill
Jun 19, 2021·Frontiers in Cell and Developmental Biology·Hongyuan JinHangyu Li
Sep 27, 2020·Journal of Hematology & Oncology·Junqing WuGuoji Guo

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Methods Mentioned

BETA
GTPases
PCR
xenograft
xenografts
GTPase
immunoprecipitation
confocal microscopy

Software Mentioned

Cell Quest
Olympus
Xcellenace
- ASW
FV10

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