Due to their biological stability and diverse cargo,
exosomes facilitate intercellular communication, thereby remodeling
the tumor microenvironment (TME) and driving disease progression
(11-17). Furthermore, exosomes offer dual
potential as diagnostic biomarkers for cancer and as drug delivery
vehicles (18-20). While various Rab proteins
isoforms perform specific regulatory functions at different stages
of exosome biogenesis (21).
Among these, Rab27 is recognized as a key molecular switch that
directly governs exosome secretion and is widely implicated in the
progression of diverse pathological conditions, including cancer,
immune-related disorders (for example, rheumatoid arthritis and
inflammatory bowel disease), neurological conditions (for example,
Parkinson's disease), metabolic and endocrine diseases (for
example, diabetes) and cardiovascular diseases (22-26). Although the role of Rab27 in
regulating exosome secretion has been reported, a systematic
overview of how Rab27 contributes to tumorigenesis and cancer
progression via exosome secretion, as well as its translational
potential as a diagnostic biomarker and therapeutic target, is
lacking. The present review systematically summarizes the molecular
mechanisms underlying Rab27-mediated exosome secretion in tumors
and highlights critical issues that must be addressed to achieve
therapeutic benefits by targeting Rab27.
Rab27 belongs to the Rab protein family and exists
in two isoforms in humans: Rab27a and Rab27b (27,28). Rab27a (221 aa) shares 61%
identity with Rab27b (218 aa) at the nucleotide level within the
open reading frame and 71% identity at the amino acid level
(29). The differences are
located mainly at the carboxy terminus (30). Structurally, both Rab27a and
Rab27b contain four GTP binding sites (16-24 aa, 74-78 aa, 133-136
aa and 163-165 aa) (31).
Moreover, they have a shared effector region (38-46 aa). The first
structural distinction between Rab27a and Rab27b lies in the
disordered regions (31).
Compared with Rab27a, Rab27b has a longer disordered region, mainly
at the carboxy terminus. Second, slight disparities in the
post-translational modification (PTM) sites of Rab27a and Rab27b
exist. Compared with Rab27b, Rab27a has more ubiquitination sites
(31,32). Moreover, the expression patterns
of Rab27a and Rab27b differ markedly across various cancer types.
For example, in certain malignancies, the expression of Rab27a is
upregulated, whereas that of Rab27b is downregulated, and in other
malignancies, the opposite pattern is observed. This differential
expression highlights the heterogeneity of the regulation of Rab27
expression in cancer (33)
(Fig. 1 and Table I).
As previously reported, Rab family proteins can be
anchored to membrane-structured suborganelles, and Rab27a and
Rab27b are no exception (30,34-36). However, some subtle differences
exist. Rab27a is distributed in a relatively large number of
subcellular organelles (30).
Specifically, Rab27a is localized to melanosomes, secretory
granules, late endosomes and lysosomes (37,38), whereas Rab27b is considered to be
localized to the membrane of Golgi stacks and vesicles located in
the trans-Golgi network (TGN) area, secretory granules and late
endosomes (30,39). The distinct subcellular
localization of Rab27 contributes critically to exosome biogenesis
and secretion by mediating specific interactions with a range of
effector proteins (23)
(Fig. 2).
Small extracellular vesicles (EVs), including
exosomes, microvesicles and small ectosomes, are generated through
the outward growth of the plasma membrane (PM) (40-42). Currently, there is no clear
demarcation between EVs and exosomes (43,44). In the present study, the term
'exosomes' was used to denote EVs with biological activity.
Exosomes are small vesicles with a diameter of 40-160 nanometers
and are characterized by a bi-layered lipid membrane (45). They play a critical role as
mediators of intercellular communication by transferring bioactive
cargo. The proteins, nucleic acids, lipids, metabolites, and even
organelles such as mitochondria within them are transported to
recipient cells, thereby influencing their biological functions
(46-52). The production of exosomes is
linked to the formation of multivesicular bodies (MVB) within cells
(53-55). Initially, the PM undergoes
endocytosis, or 'inward budding', to form early-sorting endosomes
(ESEs); the TGN and the endoplasmic reticulum also contribute to
their biogenesis. ESEs subsequently mature within the cell into
late-sorting endosomes and MVBs. These MVBs then fuse with the cell
membrane, and the intraluminal vesicles (ILVs) are expelled from
the cell through exocytosis; subsequently, the expelled ILVs become
exosomes (56-58).
Exosome biogenesis primarily involves endosomal
sorting complex required for transport (ESCRT)-dependent and
ESCRT-independent mechanisms (57,59-61). ESCRTs consist of five complexes,
including ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III and VPS4 (62,63). First, ubiquitinated cargo is
recognized and bound by the ESCRT-0 complex. It is then transferred
to the ESCRT-I and ESCRT-II complexes for sorting and processing,
ensuring the selective incorporation of specific cargo into the
ILV. The ESCRT-III complex subsequently mediates membrane curvature
and scission of the endosomal membrane, leading to ILV formation
(60,64-66). Additionally, VPS4 supplies energy
for this process by hydrolyzing ATP (67).
Rab protein-mediated exosome secretion is among the
important steps in the ESCRT-independent mechanism (21,68,69). For instance, Rab5 is involved in
the formation and transport of early endosomes, whereas Rab7 is
involved in the maturation of MVBs and serves as a critical
regulator of the fusion of MVBs with lysosomes, playing an
essential role in lysosome biogenesis (70-73). Rab proteins can interact with the
cytoskeleton and mediate the transport of exosomes along the
cytoskeleton (74,75). Rab proteins collaborate with
other proteins involved in membrane fusion, such as soluble
N-ethylmaleimide-sensitive factor attachment protein receptors
(SNAREs) proteins (an essential family of proteins that mediate the
fusion of MVBs with the PM), to promote the fusion of exosomal
membranes with cell membranes (76,77). Moreover, Rab family proteins are
associated with the cell membrane regions involved in exosome
secretion (78,79). Studies have shown that Rab11 and
Rab35 function in early or recycling endosomes (80-82). Rab11 can regulate
calcium-dependent MVB-PM fusion, thereby promoting the secretion of
exosomes (83). Interestingly, a
recent study has shown that accessory ESCRT-III can regulate the
formation of Rab11 and exosomes containing Rab11a through an
ESCRT-dependent mechanism and does not rely on the
ubiquitination/deubiquitination cycle for cargo loading (84). Rab35 and its GTPase-activating
protein (GAP) can mediate the binding of endocytic vesicles to the
PM, thereby regulating the secretion of exosomes (85). Research has indicated that Rab37
is involved in apical exosome secretion, whereas Rab39 is a
specific regulator of basolateral exosome secretion (86).
Notably, the role of Rab27 in exosome secretion
cannot be ignored. Rab27 can mediate the binding of MVBs to the PM
and the secretion of exosomes (87,88). Research has demonstrated that
Rab27a mediates the transport of MVBs to the PM (89). Moreover, Rab27a is localized to
peripheral CD63-positive MVBs, preventing MVBs from fusing with one
another or with other types of vesicles. This, in turn, promotes
the fusion of MVBs with the PM (30). Rab27a can regulate the dynamics
of cortical actin at the docking sites of MVBs by inhibiting the
localization of coronin 1b (90). Rab27b is localized in the
perinuclear region and mediates the transfer of MVBs from the TGN
to the membrane. Additionally, Rab27b can promote the maintenance
of MVBs at the cell periphery by regulating their transfer from
microtubules to the actin-rich PM (57). The regulation of exosome
secretion mediated by Rab is also intertwined with autophagy,
resulting in the formation of a complex and coordinated regulatory
network. Rab-dependent intracellular trafficking controls the
sorting and transport of MVBs, which not only directs the transport
and release of exosomes at the cell surface but also promotes the
fusion of autophagosomes with MVBs through the recruitment of
autophagy-related proteins (ATGs). This process mediates the
selective loading of exosomal cargoes, including inflammatory
factors, microRNAs and ATGs (91-94).
Rab27 typically requires cooperation with other Rab
proteins to perform its functions. For instance, in tumor cells,
Rab5 mediates the sorting of PD-L1 into endocytic vesicles, whereas
Rab27 facilitates the subsequent secretion of exosomal PD-L1. Their
synergistic action reduces the surface expression of PD-L1, thereby
enhancing the cytotoxic activity of T cells against tumors
(87). Evidence has suggested
that the cooperative interaction between Rab27a and Rab3a may
represent a critical step in vesicle trafficking. Rab27a can bind
to Rabphilin3A to form a complex, which mediates the transport of
vesicles toward the PM while recruiting a GEF to catalyze the
activation of Rab3a. Activated Rab3a then associates with
Rabphilin3A, further recruiting the SNARE complex, which ultimately
triggers the fusion of vesicles with the PM (95,96). Furthermore, Rab27 can cooperate
with Rab35 to promote the formation of MVBs (97). Conversely, Rab27 also has
antagonistic interactions with certain Rab proteins. In mast cells,
Rab37, Munc13-4 and Rab27 can form a complex, counteracting the
vesicle-priming activity of Rab27-Munc13-4 (98). In the context of Sjögren's
syndrome, an antagonistic relationship between Rab3D and Rab27 has
been identified, in which the relative activities of these two
proteins in secretory vesicles correlate with the enzymatic
activity of secretory vesicle cathepsin S in the tears of patients
(99). In addition, the
abundance of ceramides, a class of lipid signaling molecules, is
positively correlated with exosome biogenesis. Proteins in the
tetraspanin family, which form a complex with syntenin and
participate in the sorting of exosomal cargo and modulate membrane
curvature, are both critically involved in the exosome secretion
process (100-104) (Fig. 3).
In the TME, exosomes serve as critical mediators of
intercellular communication between tumor cells and non-tumor cells
(105,106). They not only reshape the
extracellular matrix, tumor vasculature and immune microenvironment
but also modulate the physical and chemical properties of the TME
and induce the malignant differentiation of nontumor cells (such as
stellate cells and adipocytes) (107-113). Given the pivotal role of
exosomes in intercellular communication within the TME, the role of
Rab27 as a key regulator of exosome secretion indicates that not
only is it a molecular switch for exosome secretion from tumor
cells but also it may be a key molecule in regulating the overall
communication of the TME.
Although the molecular mechanism of exosome
biogenesis remains incompletely understood, the expression of the
Rab27 protein as a key molecular switch that governs exosome
biogenesis has emerged as an important approach for constructing a
cell model of differential exosome secretion. Research has
indicated that in hepatocellular carcinoma (HCC) cells,
overexpression of Rab27a increases exosome secretion (114). Conversely, the inhibition of
SDC4 and Rab27a by mutant β-catenin reduces exosome secretion,
thereby facilitating immune escape and cancer cell communication in
HCC (115). Moreover, in
primary breast cancer (BC) cells, the suppression of Rab27a or
Rab27b expression can reduce the secretion of exosomes by primary
BC cells (116). Similarly,
Hannafon et al (117)
reported that in BC, silencing Rab27a expression significantly
decreased the secretion of exosomes, inhibited the antiangiogenic
effect of docosahexaenoic acid on endothelial cells, and promoted
tumor angiogenesis. In melanoma, silencing Rab27a was also shown to
reduce exosome secretion (118). In addition to its role in tumor
diseases, Rab27 also plays a role in regulating exosome secretion
in other disorders. For instance, enterovirus A71 interacts with
Rab27a through non-structural protein 3A, which can decrease Rab27a
ubiquitination and promote exosome secretion (119). In cardiomyocytes, activation of
the AKT/Rab27a signaling pathway can promote the secretion of
inflammatory exosomes (120).
These findings indicate that Rab27 plays a crucial role in the
regulation of exosome secretion. Because exosome secretion is a
complex physiological process, altering the expression or
interaction of Rab27 with other exosome marker proteins (for
example, tetraspanin superfamily members and the Rho family of
small GTPases) could be more effective for regulating exosome
secretion. For instance, Linc01703 can facilitate the secretion of
CD81+ exosomes via the formation of the
Rab27a/SYTL1/CD81 complex (121).
Rab27a and Rab27b are oncogenes. They can regulate
diverse malignant biological behaviors of cancer cells via
different molecular mechanisms (122,123). Research on melanoma revealed
that silencing Rab27 expression significantly decreased the levels
of various intracellular proteins associated with cancer cell
proliferation, invasion, angiogenesis, adhesion and
epithelial-mesenchymal transition (EMT). These findings indicate
that Rab27 is closely linked to a variety of malignant biological
behaviors of cancer cells (124). The aforementioned study
demonstrated that silencing Rab27 in mice bearing brain tumors
induced vascular malformations and increased tumor vascular
permeability, thereby facilitating immune cell infiltration across
the blood-brain barrier and enhancing the efficacy of anti-brain
tumor immunotherapy (125).
Most studies have demonstrated that Rab27 is closely associated
with the proliferation, migration and invasion of cancer cells. Li
et al reported that Rab27a promoted the proliferation,
migration and invasion of colorectal cancer (CRC) cells (126). In vitro experiments have
shown that Rab27a can increase the proliferation, migration and
invasion of oral squamous cell carcinoma cells. The underlying
molecular mechanism might be related to the regulation of
ZDHHC13-mediated epidermal growth factor receptor palmitoylation
and membrane retention by Rab27a (127). Moreover, Rab27a can increase
the proliferation and migration of bladder cancer cells by
activating the NF-κB pathway. It can also inhibit apoptosis,
thereby inducing chemotherapy resistance (128). Rab27b can interact with ZDHHC9
to regulate NRAS palmitoylation and facilitate the progression of
myeloid leukemia (129).
Interestingly, in a xenograft mouse model, Nambara et al
(130) demonstrated that Rab27b
promoted the peritoneal metastasis of gastric cancer (GC) cells.
However, it did not affect the proliferation or invasion of cancer
cells in vitro (130).
These findings suggest that in a mouse model, Rab27 may promote
peritoneal metastasis through exosome-mediated remodeling of the
TME rather than through its direct effect on the cancer cells
themselves.
Nevertheless, the function of Rab27 is not absolute.
Its tumor-suppressive role in PDAC contrasts sharply with its
aforementioned tumor-promoting functions, indicating its remarkable
functional plasticity and dependence on the TME. The expression
level of Rab27a in PDAC gradually decreases with disease
progression. Ablation of Rab27a in genetically engineered mouse
models promotes liver metastasis of cancer cells, supporting a
tumor-suppressive role for Rab27a in PDAC (141). This may be closely linked to
PDAC-specific epigenetic regulation. Hypermethylation of the SMC3
gene in PDAC tissues represses its expression, thereby weakening
the binding of SMC3 to the promoter and enhancer regions of Rab27a
and reducing the transcriptional activity of Rab27a, ultimately
resulting in downregulated Rab27a expression in PDAC (141). In addition, disparities in the
genetic background of different tumor cell types may also
contribute to the divergent functions of Rab27. Collectively, these
findings suggest that Rab27 acts neither as a pure oncoprotein nor
as a strict tumor suppressor and that its function is coordinately
modulated by the intrinsic properties of tumor cells, the TME, and
disease stage. These findings provide a theoretical basis for
targeting Rab27 and exosome-mediated intercellular communication
for precision cancer therapy. Clinical intervention should consider
tumor type-specific microenvironmental characteristics and
molecular regulatory mechanisms to develop individualized
therapeutic regimens, thereby overcoming the limitations of
conventional single-target therapies (Table II).
The expression of Rab27 in tumor tissues is a
valuable biomarker for predicting poor prognosis across various
malignant neoplasms. In gastric carcinoma research, Rab27b
expression has been found to be negatively correlated with both
overall survival and recurrence-free survival, indicating its
potential as a prognostic biomarker for adverse outcomes (130). With respect to lung squamous
cell carcinoma, increased Rab27b expression has been identified as
a potential negative prognostic indicator for patients with NSCLC
(142). In pancreatic cancer
studies, Rab27b expression has been shown to be associated with
poor survival outcomes in a subgroup of patients who may exhibit
favorable responses to adjuvant chemotherapy (143). Notably, the roles of Rab27a and
Rab27b are distinct in cancer tissues with different pathological
characteristics. A study by An et al (144) further indicated that Rab27a and
Rab27b may serve as potential biomarkers for predicting lymph node
metastasis and prognosis in patients with GC. In GC tissues, Rab27a
is highly expressed and predominantly localized in the nucleus, and
its expression level is significantly positively correlated with
lymph node metastasis. Rab27b is also globally overexpressed, is
distributed mainly in the cytoplasm and PM, and has pathological
subtype-specific prognostic value (144). In well-differentiated GC, high
Rab27b expression is associated with reduced patient survival,
whereas in poorly differentiated adenocarcinoma, low Rab27b
expression predicts a worse prognosis (144). However, the aforementioned
study lacked comparative analyses of Rab27a and Rab27b expression
and localization in paired adjacent non-tumor tissues, which may
explain the divergent prognostic performance of these two proteins
in GCs with distinct differentiation statuses. In a study by
Kottorou et al (145),
the expression of both Rab27a and Rab27b was shown to be
downregulated in CRC tissues and correlated with poor patient
prognosis. Notably, low Rab27b expression is closely associated
with advanced tumor stage, lymph node metastasis, and distant
metastasis, whereas high Rab27b expression is linked to poor tumor
differentiation and high malignancy (145). These findings suggest that
Rab27 may act as a double-edged sword in relation to cancer
progression. This phenomenon may be attributed to tumor
heterogeneity and the bidirectional nature of signaling networks
downstream of Rab27a and could also involve differential responses
of tumor cells to diverse external stimuli, including chemotherapy
and targeted therapy (Table
III).
In the field of cancer therapy, as a key regulator
of exosome secretion, Rab27 holds great promise for targeted
therapeutic applications. By mediating exosome secretion and
remodeling the TME, targeting Rab27 may not only directly suppress
the malignant phenotypes of tumor cells but also improve vascular
function and reverse the immunosuppressive state (125). Currently, therapeutic
strategies targeting Rab27 are under active development and are
expected to provide new breakthroughs for precision cancer
therapy.
Given the critical role of Rab27 in tumor
progression and its complex downstream regulatory networks,
downregulating Rab27 expression using gene silencing technologies
is theoretically associated with favorable antitumor effects.
Researchers have strategically utilized the unique tropism of
Epstein-Barr virus (EBV) for human B cells by incorporating Rab27a
small interfering RNA into inactivated EBV particles, which
effectively reduces the release of CD19+ exosomes from B
cells, consequently enhancing the antitumor efficacy of
chemotherapeutic interventions (146). Furthermore, targeting Rab27 in
combination with other agents has synergistic effects. Depletion of
Rab27a diminishes tumor-derived exosome secretion, reverses hepatic
metabolic reprogramming, alleviates chemoresistance, and reduces
adverse effects of chemotherapy (147). In BC cells, silencing Rab27a
decreases 6J1-induced PD-L1 secretion in exosomes, potentiates
antitumor immune responses, and improves therapeutic efficacy
(87). Nevertheless, RNA
interference-based strategies generally suffer from insufficient
target specificity and poor in vivo stability, restricting
their clinical application to local administration or reliance on
highly efficient delivery carriers (148). In addition, inhibition of a
single target may trigger compensatory signaling pathways,
resulting in suboptimal therapeutic outcomes (28,149).
Given the limitations associated with
single-targeted inhibition of Rab27, the development of
multitarget, multi-pathway small-molecule strategies has distinct
advantages. Tipifarnib, an inhibitor of exosome biogenesis,
simultaneously targets Rab27a, nSMase2 and ALIX. By suppressing the
PTM of Rab27 and acting cooperatively on multiple core proteins
involved in exosome biogenesis, it overcomes acquired resistance
resulting from single-target interventions (150). However, the pharmacokinetic
properties and toxicological profiles of such synthetic small
molecules still require comprehensive evaluation. Natural
small-molecule products have shown promising translational
potential in targeting Rab27 because of their multitarget
characteristics and favorable cost effectiveness (151). Acorus calamus
effectively suppresses exosome secretion in TNBC cells through dual
targeting of Rab27a and nSMase2 (152). Resveratrol reduces exosome
secretion by suppressing Rab27a expression, thereby inhibiting
proliferation, migration and EMT in Huh7 cells and blocking HCC
progression. Furthermore, resveratrol-induced exosomes further
suppress the malignant phenotypes of tumor cells by inhibiting
β-catenin nuclear translocation and autophagy activation (153). In the future, identifying and
structurally optimizing the core pharmacophores that target Rab27
from natural products is expected to emerge as an important
direction for the development of drugs targeting Rab27.
In addition to directly targeting Rab27, disrupting
its interaction with downstream effector molecules or blocking
downstream signaling pathways represents an effective intervention
strategy. The novel compound BHMPS
[(E)-N-benzyl-6-(2-(3,4-dihydroxy-benzylidene)hydrazinyl)-N-methylpyridine-3-sulfonamide]
has been identified as an effective inhibitor of the Rab27a-Slp4
interaction. The inhibition of Rab27a-mediated exosome secretion
represents a promising therapeutic strategy for suppressing BC
metastasis and invasion (154).
Molecular studies have revealed that MUC1-C interacts with the
Rab27a protein and that targeted inhibition of MUC1-C expression
significantly suppresses the secretion of MICA/B-containing
exosomes (155). Notably, both
aforementioned strategies remain at the basic research stage.
Camptothecin, a widely used chemotherapeutic agent, targets Topo I
to block DNA replication and repair and induce apoptosis in cancer
cells (156). Moreover, it has
been shown that camptothecin can also inhibit proliferation and
migration in head and neck squamous cell carcinoma by blocking the
Rab27a-mediated activity of the PI3K/AKT pathway (157). These findings support the
feasibility of drug repurposing for cancer therapy.
As inhibitors of exosome biogenesis and secretion,
Nexinhib20 and GW4869 exhibit considerable potential in antitumor
therapy. Nexinhib20 suppresses exosome secretion by specifically
blocking the interaction between Rab27a and JFC1, whereas GW4869
effectively inhibits the expression of nSMase2 and thereby reduces
exosome biogenesis (158-160). It has been demonstrated that
combining Nexinhib20 or GW4869 with cisplatin/etoposide enhances
the inhibitory effects of first-line chemotherapy against small
cell lung cancer cells (161).
Moreover, Nexinhib20 selectively inhibits granule and exosome
release without compromising critical neutrophil functions such as
phagocytosis and neutrophil extracellular traps formation,
theoretically conferring a lower risk of immunosuppression
(162). However, both agents
remain at the preclinical stage of cellular and animal models, and
their safety profiles and pharmacokinetic properties require
further validation. Additionally, strategies to achieve selective
inhibition of tumor-derived exosomes rather than those from normal
cells remain to be addressed.
While several Rab27-targeted strategies have been
developed, their safety profiles require critical evaluation. Rab27
is widely involved in physiological vesicle secretion in normal
cells and regulates key processes, including immune cytokine
release, insulin secretion and neurotransmission. Non-specific
targeting may readily lead to multisystem side effects such as
immune dysregulation and metabolic disorders (122,163). Therefore, a balance must be
maintained between therapeutic efficacy and target selectivity in
the development of Rab27-targeted antitumor agents. Although
existing studies have indicated that resveratrol at effective doses
does not significantly affect Rab27 expression in normal cells, its
selectivity and potential toxic side effects in complex human
physiological environments still require careful evaluation
(153,164). Furthermore, the regulation of
Rab27 by camptothecin, resveratrol, and Acorus calamus is
concentration-dependent. How to maintain potent antitumor activity
while avoiding interference with insulin secretion and
neurotransmission represents an urgent clinical translation
challenge (152,153,157) (Fig. 4 and Table IV).
Typically, Rab27a and Rab27b can regulate the
malignant progression of tumors by promoting the secretion of
exosomes (149,163). Interestingly, the two play
different roles in the process of exosome secretion. Rab27a is
localized to peripheral CD63-positive MVBs and is essential for
mediating the fusion of MVBs with the PM (30). By contrast, Rab27b is
predominantly located in the perinuclear region, where it regulates
the transfer of MVBs from microtubules to the actin-rich cortex,
facilitating membrane turnover from the TGN to MVBs (30). While the majority of studies have
identified Rab27 as an oncogene and a molecular switch for exosome
release, alternative perspectives have emerged. For instance,
recent research has indicated that the impact of Rab27a on the
migration and invasion of melanoma cell lines may be contingent
upon the unique characteristics of the cell line and appears to be
independent of exosome secretion (165). These findings not only reveal
the complex roles of Rab27 in tumors and exosomes but also provided
a direction for further exploration of its underlying mechanisms
and application value.
The Rab27 protein plays a pivotal role in tumor
biology, primarily through its regulation of exosome secretion,
which significantly influences tumor cell proliferation, invasion
and metastatic potential. Its expression levels are strongly
correlated with tumor initiation, progression and clinical
outcomes. The scientific community has reached a consensus that the
modulation of Rab27 expression directly impacts exosome secretion
dynamics. However, the precise molecular mechanisms underlying
Rab27-mediated exosome biogenesis and secretion warrant further
comprehensive investigation. Considering the critical role of
exosomal genetic cargo in tumor regulation, exploring whether Rab27
facilitates the selective enrichment of specific genetic materials
within exosomes, thereby influencing tumor progression, is
imperative. Beyond its established potential as a diagnostic
biomarker and therapeutic target in oncology, the upregulation of
Rab27 expression may offer a novel approach for the efficient
production of engineered exosomes, presenting innovative strategies
for the large-scale preparation of artificial exosomes for
therapeutic applications.
Not applicable.
MT and ZZ drafted the manuscript and prepared the
figures. HD, ST, MS, XJ, QP, LO and ZR helped collect the related
studies and participated in discussions. YZ and QL designed the
review and revised the manuscript. All authors read and approved
the final version of the manuscript. Data authentication is not
applicable.
Not applicable.
Not applicable.
The authors declare that they have no competing
interests.
Not applicable.
The present study was supported in part by the National Natural
Science Foundation of China (grant nos. 82472882, 82302987 and
82303534), the Natural Science Foundation of Hunan (grant nos.
2025JJ30047, 2024JJ4025, 2023ZJ1122, 2023JJ60469, 2023JJ40413,
2023JJ30372 and 2023JJ30375), the Science and Technology Innovation
Program of Hunan (grant nos. 2023RC3199, 2023SK4034 and
2023RC1073), the National Key Clinical Specialty Scientific
Research Project (grant nos. Z2023086 and Z2023017), the Hunan
Provincial Health High-Level Talent Scientific Research Project
(R2023040 and R2023093), and the Research Project of the Health
Commission of Hunan (grant nos. 20255845 and 20255433).
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