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

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 stemness.
Authors	Shu-Huei Cho, I-Ying Kuo, Pei-Jung Frank Lu, Hong-Tai Tzeng, Wu-Wei Lai, Wu-Chou Su, Yi-Ching Wang
Journal	Cell death & disease (Cell Death Dis) Vol. 9 Issue 9 Pg. 868 (08 29 2018) ISSN: 2041-4889 [Electronic] England
PMID	30158579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Biomarkers, Tumor Intercellular Signaling Peptides and Proteins Membrane Proteins Octamer Transcription Factor-3 SFRP1 protein, human Rab37 protein, human rab GTP-Binding Proteins
Topics	Aged Animals Biomarkers, Tumor (metabolism) Cell Line, Tumor Exocytosis (physiology) Female Gene Expression Regulation, Neoplastic (physiology) Humans Intercellular Signaling Peptides and Proteins (metabolism) Lung Neoplasms (metabolism, pathology) Male Membrane Proteins (metabolism) Mice Mice, Inbred BALB C Octamer Transcription Factor-3 (metabolism) Prognosis Wnt Signaling Pathway (physiology) rab GTP-Binding Proteins (metabolism)

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