Ask about this productRelated genes to: RAB4A antibody
- Gene:
- RAB4A NIH gene
- Name:
- RAB4A, member RAS oncogene family
- Previous symbol:
- RAB4
- Synonyms:
- HRES-1/RAB4
- Chromosome:
- 1q42.13
- Locus Type:
- gene with protein product
- Date approved:
- 1989-09-11
- Date modifiied:
- 2016-10-05
Related products to: RAB4A antibody
Related articles to: RAB4A antibody
- The relapse rate for early-stage triple-negative breast cancer (TNBC) is significantly higher than that of other breast cancer subtypes. To reduce the relapse rate, we evaluated the relevance of targeting Rab4A to inhibit the increase in cancer cell invasion induced by radiotherapy (RT). The ability of cancer cells to invade into adjacent tissues correlates with the proteolytic activity of membrane type 1 matrix metalloproteinase (MT1-MMP) on their surface, whose turnover is regulated by Rab4A. When RAB4A was downregulated using shRNA in the TNBC cells D2A1 and MDA-MB-231, a significant reduction in the proteolytic activity of MT1-MMP and the invasion capacity of these TNBC cells were measured. Plasma samples from six early-stage TNBC patients were collected before RT and after the fourth radiation dose. Plasma samples collected during RT from three of these patients increased the invasiveness of TNBC cells, compared to plasma collected before RT. Of them, two experienced a recurrence of their cancer, while the third patient had not yet completed the 5-year follow-up. The downregulation of RAB4A inhibited the RT-induced increase in cancer cell invasion. In contrast, in the three patients who did not relapse after 5-year follow-up, plasma collected during RT did not significantly increase the invasiveness of the MDA-MB-231 cells, compared to their plasma collected before RT. The decrease in RAB4A expression did not result in a significant difference in the invasiveness of cancer cells when incubated with plasma collected before or during RT from these patients. Metastatic development was observed when D2A1 cells were preincubated before i.v. injection in Balb/c mice with plasma collected during RT from a patient who experienced early cancer relapse; this was also inhibited by downregulating RAB4A. In summary, our preliminary results generate the hypothesis that RT may increase cancer cell invasion and metastasis formation, which is associated with the Rab4A-mediated turnover of MT1-MMP on the cancer cell surface. - Source: PubMed
Publication date: 2026/09/15
Paquette BenoitTherriault HélèneGauthier IsabelleProvencher SawynaBourque Jean-MarcNaasri SaharOweida AymanGeha SamehLabrecque PascaleParent Jean-Luc - HSPA1A is a stress-inducible molecular chaperone that localizes to the plasma membrane (PM) of heat-shocked and cancer cells, where its membrane-associated form contributes to therapeutic resistance, membrane stabilization, and immune modulation. Because HSPA1A lacks a signal peptide, it does not follow the classical secretory pathway; instead, it reaches the PM through unconventional routes whose vesicular intermediates and intracellular lipid requirements remain largely undefined. Here, we show that following heat shock, HSPA1A undergoes coordinated redistribution across the endo-lysosomal network. It transiently associates with PI(3)P-enriched early endosomes, progresses through Rab4A- and Rab4B-positive recycling endosomes, and accumulates in LAMP1-positive lysosomes, while avoiding degradative and slow-recycling routes. Pharmacological inhibition of the ER-Golgi pathway did not affect HSPA1A's PM localization, while disruption of endosomal maturation and lysosomal function resulted in significant reductions. Heat shock drives a progressive increase in lysosomal Bis(monoacylglycero)phosphate (BMP) immunoreactivity, and pharmacological BMP accumulation increased PM-HSPA1A, whereas intracellular antibody-mediated BMP blockade reduced it, identifying BMP-enriched lysosomes as regulatory hubs that govern HSPA1A PM competence. Using a rapamycin-inducible compartment-specific phosphatase system, we further demonstrate that PI(4)P is required not only at the PM for final docking but within early endosomes, late endosomes, and lysosomes, establishing a distributed PI(4)P requirement across the endosomal network. Together, these findings define a lipid-gated vesicular trafficking mechanism for HSPA1A PM localization and identify lysosomal BMP and endosomal PI(4)P as additional regulatory layers relevant to cancer cells in which constitutive lipid remodeling may sustain membrane-associated HSPA1A and its pro-survival functions. - Source: PubMed
Publication date: 2026/08/25
Low JensenCuaresma Azalea BlytheMartin Clarisse KBadolian AllenAlSebaye MahaStahelin Robert VNikolaidis Nikolas - Extracellular vesicles (EVs) secreted by cancer cells actively modulate the tumor microenvironment, thereby promoting cancer progression. Transforming growth factor-β (TGF-β) signaling has been implicated in the regulation of EV biogenesis, yet the molecular mechanisms underlying this process have only recently begun to emerge. In this study, we investigated TGF-β-responsive mediators that regulate EV release in lung, breast, and ovarian carcinoma cells by modulating the expression and activity of genes associated with EV biogenesis, including components of the ESCRT machinery, tetraspanins, and Rab GTPases. We found that TGF-β selectively enhances the mRNA expression of PDCD6IP (ALIX), CD81, ARF6, and RAB4A in a cell type-specific manner. R-SMAD silencing had clear negative effects on the regulation of ALIX or RAB4A, whereas AKT kinase inhibition suppressed the induction of ALIX and CD81. Additionally, TGF-β stimulation increased ALIX S-palmitoylation, consistent with enhanced ALIX-TSG101 complex formation on vesicular membranes. However, knockdown of ALIX or CD81 did not impair TGF-β-induced EV secretion. On the contrary, TGF-β-induced upregulation of RAB4A expression is functionally unique because RAB4A facilitates fast endosomal recycling, a process that limits EV release. Accordingly, silencing RAB4A significantly increased the fusion of multivesicular bodies with the plasma membrane followed by EV secretion, suggesting that TGF-β-induced RAB4A acts as a negative feedback regulator of EV release. Our findings reveal a novel mechanism by which RAB4A modulates TGF-β-driven EV production by cancer cells. - Source: PubMed
Publication date: 2026/03/30
Rodrigues-Junior Dorival MendesDoumani Maria AnastasiaFu Haovan den Bor JelleIdevall-Hagren OlofMoustakas Aristidis - Large-conductance Ca-activated potassium (BK) channels are widely expressed across human tissues and play fundamental roles in the regulation of diverse cellular processes. Dysregulation of BK channel expression or activity has been implicated in multiple pathological conditions, including cancer, where BK channel overexpression is associated with enhanced tumor cell proliferation and altered cellular dynamics. In this study, we present an integrative computational framework to identify, structurally characterize, and rationally target BK channel-associated protein-protein interactions (PPI) in breast cancer. RNA-seq differential expression analysis revealed significant overexpression of KCNMA1 in estrogen-sensitive breast cancer cells, supporting a central role for BK channels in tumor-associated phenotypes. By integrating transcriptomic data with curated interaction databases and PPI prediction methods, we constructed a breast cancer-specific interaction network centered on BK and identified ACTG2, LINGO1, and RAB4A as high-confidence interaction partners. Structural modeling and coarse-grained molecular dynamics simulations revealed stable, partner-specific interaction interfaces between BK and each interactor, identifying key residues governing complex formation. Building on these results, we present the first computational structural model of the BK-LINGO1 complex, which reveals a predominantly hydrophobic transmembrane interface consistent with the established role of LINGO1 as a regulatory accessory subunit. Leveraging this PPI interface, we designed peptide-based modulators using a structure-guided approach and identified peptide variants with enhanced conformational stability and favorable binding energetics. Overall, our work establishes a robust computational framework for mapping BK channel protein-protein interactions in breast cancer and demonstrates the feasibility of targeting these interactions through rational peptide design, opening new opportunities for the selective modulation of BK channel function in cancer. - Source: PubMed
Publication date: 2026/03/17
González-Avendaño MarielaRosales-Rojas RobertoVergara-Jaque Ariela - Platelet α-granules are lysosome-related organelles produced in megakaryocytes, the platelet precursor cells. The biogenesis of α-granules is incompletely understood but depends on common endosomal pathways. Here, we discovered GRIPAP1, a partially characterized ubiquitous protein, as a new component of the α-granule biogenesis machinery. GRIPAP1-deficient megakaryocytes showed a significant decrease of α-granule numbers and overall cargo levels. In WT megakaryocytes, fibrinogen taken up by endocytosis and newly synthesized PF4 trafficked through GRIPAP1-labeled compartments en route to α-granules. GRIPAP1 localized to endosome subdomains decorated by Rab4a and Stx12, known players in α-granule biogenesis. GRIPAP1 bound GTP-loaded Rab4a, a key interaction for GRIPAP1 recruitment to membranes. Biochemically, GRIPAP1 behaved as an elongated homodimer akin to membrane tethering factors. Consistently, artificial mislocalization of GRIPAP1 to the mitochondria was sufficient to recruit Rab4a compartments containing internalized transferrin and newly synthesized PF4 to mitochondria. Together, the data advance understanding of endosomal transport, the biogenesis of α-granules, and likely other endo-lysosomal organelles. - Source: PubMed
Publication date: 2026/02/03
Ambrosio Andrea LFebvre Hallie PSchusler Gabrielle HDi Pietro Santiago M