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1.
J Cell Biol ; 220(7)2021 07 05.
Article in English | MEDLINE | ID: mdl-33978708

ABSTRACT

Polarity is essential for diverse functions in many cell types. Establishing polarity requires targeting a network of specific signaling and cytoskeleton molecules to different subregions of the cell, yet the full complement of polarity regulators and how their activities are integrated over space and time to form morphologically and functionally distinct domains remain to be uncovered. Here, by using the model system Dictyostelium and exploiting the characteristic chemoattractant-stimulated translocation of polarly distributed molecules, we developed a proteomic screening approach, through which we identified a leucine-rich repeat domain-containing protein we named Leep1 as a novel polarity regulator. We combined imaging, biochemical, and phenotypic analyses to demonstrate that Leep1 localizes selectively at the leading edge of cells by binding to PIP3, where it modulates pseudopod and macropinocytic cup dynamics by negatively regulating the Scar/WAVE complex. The spatiotemporal coordination of PIP3 signaling, Leep1, and the Scar/WAVE complex provides a cellular mechanism for organizing protrusive structures at the leading edge.


Subject(s)
Actins/economics , Cell Polarity/genetics , Pinocytosis/genetics , Protozoan Proteins/genetics , Actins/genetics , Cell Movement/genetics , Chemotaxis/genetics , Cytoplasm/genetics , Dictyostelium/genetics , Pseudopodia/genetics , Signal Transduction/genetics
2.
J Cell Physiol ; 235(12): 9718-9728, 2020 12.
Article in English | MEDLINE | ID: mdl-32401366

ABSTRACT

The tumor-suppressive role of microRNA-216a-3p (miR-216a-3p) has been evidenced in multiple tumors. Yet, the relevance of miR-216a-3p in cervical cancer remains undermined. The current study was designed to determine the expression and potential function of miR-216a-3p in cervical cancer. Expression of miR-216a-3p was markedly decreased in cervical cancer and functional assays revealed an inhibitory effect of miR-216a-3p on the proliferation, colony formation, and invasion of cervical cancer. Actin-like 6A (ACTL6A) was identified as a target gene of miR-216a-3p. Elevated ACTL6A expression was detected in cervical cancer, and ACTL6A inhibition exhibited a tumor-suppressive effect. ACTL6A inhibition increased yes-associated protein (YAP) phosphorylation and downregulated YAP-mediated transcriptional activity. ACTL6A restoration or YAP reactivation partially abrogated the miR-216a-3p-mediated antitumor effect in cervical cancer cells. Taken together, these data demonstrate that miR-216a-3p acts as a potential tumor-suppressive miRNA in cervical cancer, which exerts its function through inhibition of YAP signaling via targeting ACTL6A.


Subject(s)
Actins/genetics , Adaptor Proteins, Signal Transducing/genetics , Chromosomal Proteins, Non-Histone/genetics , DNA-Binding Proteins/genetics , MicroRNAs/genetics , Transcription Factors/genetics , Uterine Cervical Neoplasms/genetics , Actins/economics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Chromosomal Proteins, Non-Histone/economics , DNA-Binding Proteins/economics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Neoplasm Invasiveness/genetics , Signal Transduction/genetics , Uterine Cervical Neoplasms/pathology , YAP-Signaling Proteins
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