Receptor-like cytoplasmic kinases PBL34/35/36 are required for CLE peptide-mediated signaling to maintain shoot apical meristem and root apical meristem homeostasis in Arabidopsis.

Shoot apical meristem (SAM) and root apical meristem (RAM) homeostasis is tightly regulated by CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION-related (CLE) peptide signaling. However, the intracellular signaling components after CLV3 is perceived by the CLV1-CLV3-INSENSITIVE KINASE (CIK) receptor complex and CLE25/26/45 are sensed by the BARELY ANY MERISTEM (BAM)-CIK receptor complex are unknown. Here, we report that PBS1-LIKE34/35/36 (PBL34/35/36), a clade of receptor-like cytoplasmic kinases, are required for both CLV3-mediated signaling in the SAM and CLE25/26/45-mediated signaling in the RAM. Physiological assays showed that the SAM and RAM of pbl34 pbl35 pbl36 were resistant to CLV3 and CLE25/26/45 treatment, respectively. Genetic analyses indicated that pbl34 pbl35 pbl36 greatly enhanced the SAM defects of clv2 and rpk2 but not clv1, and did not show additive effects with bam3 and cik2 in the RAM. Further biochemical assays revealed that PBL34/35/36 interacted with CLV1, BAM1/3, and CIKs, and were phosphorylated by CLV1 and BAM1. All these results suggest that PBL34/35/36 act downstream of CLV1 and BAM1/3 to mediate the CLV3 and CLE25/26/45 signals in maintaining SAM and RAM homeostasis, respectively. Our findings shed light on how CLE signals are transmitted intracellularly after being perceived by cell surface receptor complexes.

ThCr2Si2C: An Antiferromagnetic Metal with a Cr2C Square Lattice.

A quaternary compound, ThCr2Si2C, was synthesized by using the arc-melting technique. The compound adopts a tetragonal CeCr2Si2C-type crystal structure. The electronic resistivity and specific heat data exhibit metallic behavior, while the magnetic susceptibility displays a pronounced broad peak at around 370 K, indicating the antiferromagnetic phase transition. The first-principles calculations suggest A-type antiferromagnetic ordering of the Cr sublattice, which is confirmed by neutron diffraction experiments. By comparing the crystal structure of ThCr2Si2C with the isostructural Cr-based compounds, the magnetic state of Cr 3d orbital is discussed in terms of the band-filling effects and indirect spin exchange interaction.

SERKs regulate embryonic cuticle integrity through the TWS1-GSO1/2 signaling pathway in Arabidopsis.

The embryonic cuticle integrity is critical for the embryo to separate from the neighboring endosperm. The sulfated TWISTED SEED1 (TWS1) peptide precursor generated in the embryo diffuses through gaps of the nascent cuticle to the surrounding endosperm, where it is cleaved by ABNORMAL LEAF SHAPE1 (ALE1) and becomes an active mature form. The active TWS1 is perceived by receptor-like protein kinases GASSHO1 (GSO1) and GSO2 in the embryonic epidermal cells to start the downstream signaling and guide the formation of an intact embryonic cuticle. However, the early signaling events after TWS1 is perceived by GSO1/2 are still unknown. Here, we report that serk1/2/3 embryos show cuticle defects similar to ale1, tws1, and gso1/2. Genetic and biochemical analyses were performed to dissect the signaling pathway mediated by SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASEs (SERKs) during cuticle development. SERKs function with GSO1/2 in a common pathway to monitor the integrity of the embryonic cuticle. SERKs interact with GSO1/2, which can be enhanced dramatically by TWS1. The phosphorylation levels of SERKs and GSO1/2 rely on each other and can respond to and be elevated by TWS1. Our results demonstrate that SERKs may function as coreceptors of GSO1/2 to transduce the TWS1 signal and ultimately regulate embryonic cuticle integrity.

A CLE-BAM-CIK signalling module controls root protophloem differentiation in Arabidopsis.

Exogenous application of CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (CLE) peptides suppresses protophloem differentiation and leads to the consumption of the proximal root meristem. However, the exact CLE peptides and the corresponding receptor complex regulating protophloem differentiation have not yet been clarified. Through expression pattern and phylogenetic analyses, CLE25/26/45 were identified as candidate peptides. Further genetic analyses, physiological assays and specific protophloem marker observations indicated that CLE25/26/45, BARELY ANY MERISTEM1/3 (BAM1/3) and CLV3 INSENSITIVE KINASEs (CIKs) are involved in regulating protophloem differentiation. The cle25 26 45 and cik2 3 4 5 6 mutation can greatly rescue the root defects of brevis radix (brx) and octopus (ops) mutants. The protophloem differentiation and proximal root meristem consumption of clv1 bam1 3 and cik2 3 4 5 6 were insensitive to CLE25/26/45 treatments. cle25 26 45, clv1 bam1 3 and cik2 3 4 5 6 displayed similar premature protophloem. In addition, CLE25/26/45 induced the interactions between BAMs and CIKs in vivo. Furthermore, CLE25/26/45 enhanced the phosphorylation levels of CIKs, which were greatly impaired in clv1 bam1 3 mutant. Our work clarifies that the CLE25/26/45-BAM1/3-CIK2/3/4/5/6 signalling module genetically acts downstream of BRX and OPS to suppress protophloem differentiation.

CIK Receptor Kinases Determine Cell Fate Specification during Early Anther Development in Arabidopsis.

Appropriate cell division and differentiation ensure normal anther development in angiosperms. BARELY ANY MERISTEM 1/2 (BAM1/2) and RECEPTOR-LIKE PROTEIN KINASE2 (RPK2), two groups of leucine-rich repeat receptor-like protein kinases, are required for early anther cell specification. However, little is known about the molecular mechanisms underlying these two RLK-mediated signaling pathways. Here, we show that CLAVATA3 INSENSITIVE RECEPTOR KINASEs (CIKs), a group of novel coreceptor protein kinase-controlling stem cell homeostasis, play essential roles in BAM1/2- and RPK2-regulated early anther development in Arabidopsis thaliana The archesporial cells of cik1/2/3 triple and cik1/2/3/4 quadruple mutant anthers perform anticlinal division instead of periclinal division. Defective cell division and specification of the primary and inner secondary parietal cells occur in these mutant anthers. The disordered divisions and specifications of anther wall cells finally result in excess microsporocytes and a lack of one to three parietal cell layers in mutant anthers, resembling rpk2 or bam1/2 mutant anthers. Genetic and biochemical analyses indicate that CIKs function as coreceptors of BAM1/2 and RPK2 to regulate archesporial cell division and determine the specification of anther parietal cells.

TCP7 functions redundantly with several Class I TCPs and regulates endoreplication in Arabidopsis.

TCP (TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR) proteins, a family of plant-specific transcription factors, play important roles in many developmental processes. However, genetic and functional redundancy among class I TCP limits the analysis of their biological roles. Here, we identified a dominant-negative mutant of Arabidopsis thaliana TCP7 named leaf curling-upward (lcu), which exhibits smaller leaf cells and shorter hypocotyls than the wild type, due to defective endoreplication. A septuple loss-of-function mutant of TCP7, TCP8, TCP14, TCP15, TCP21, TCP22, and TCP23 displayed similar developmental defects to those of lcu. Genome-wide RNA-sequencing showed that lcu and the septuple mutant share many misexpressed genes. Intriguingly, TCP7 directly targets the CYCLIN D1;1 (CYCD1;1) locus and activates its transcription. We determined that the C-terminus of TCP7 accounts for its transcriptional activation activity. Furthermore, the mutant protein LCU exhibited reduced transcriptional activation activity due to the introduction of an EAR-like repressive domain at its C-terminus. Together, these observations indicate that TCP7 plays important roles during leaf and hypocotyl development, redundantly, with at least six class I TCPs, and regulates the expression of CYCD1;1 to affect endoreplication in Arabidopsis.

Glucose Intake Alters Expression of Neuropeptides Derived from Proopiomelanocortin in the Lateral Hypothalamus and the Nucleus Accumbens in Fructose Preference Rats.

To study the neuroendocrine mechanism of sugar preference, we investigated the role of glucose feeding in the regulation of expression levels of neuropeptides derived from proopiomelanocortin (POMC) in the lateral hypothalamus (LH) and nucleus accumbens (NAc) in fructose preference rats. Fructose preference rats were induced by using the lithium chloride backward conditioning procedure. The fructose preference was confirmed by the two-bottle test. The drinking behavior of rats was assessed by the fructose concentration gradient test. The preference of 10% glucose or 0.1% saccharine was assessed, and the expression levels of neuropeptides derived from POMC in the LH and the NAc in fructose preference rats were measured by Western blot analysis. Fructose preference rats displayed a greater fructose preference than control rats. Furthermore, fructose preference rats preferred glucose solution rather than saccharine solution, while control rats preferred saccharine solution rather than glucose solution. The expression levels of neuropeptides derived from POMC in the LH and the NAc were changed by glucose but not saccharine intake. In summary, the data suggests that glucose intake increases the expression of neuropeptides derived from POMC in the LH and the NAc in fructose preference rats.

CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

The Dof transcription factor COG1 acts as a key regulator of plant biomass by promoting photosynthesis and starch accumulation.

Photosynthetic efficiency is the primary determinant of crop yield, including vegetative biomass and grain yield. Manipulation of key transcription factors known to directly control photosynthetic machinery can be an effective strategy to improve photosynthetic traits. In this study, we identified an Arabidopsis gain-of-function mutant, cogwheel1-3D, that shows a significantly enlarged rosette and increased biomass compared with wild-type plants. Overexpression of COG1, a Dof transcription factor, recapitulated the phenotype of cogwheel1-3D, whereas knocking out COG1 and its six paralogs resulted in a reduced rosette size and decreased biomass. Transcriptomic and quantitative reverse transcription polymerase chain reaction analyses demonstrated that COG1 and its paralogs were required for light-induced expression of genes involved in photosynthesis. Further chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that COG1 can directly bind to the promoter regions of multiple genes encoding light-harvesting antenna proteins. Physiological, biochemical, and microscopy analyses revealed that COG1 enhances photosynthetic capacity and starch accumulation in Arabidopsis rosette leaves. Furthermore, combined results of bioinformatic, genetic, and molecular experiments suggested that the functions of COG1 in increasing biomass are conserved in different plant species. These results collectively demonstrated that COG1 acts as a key regulator of plant biomass by promoting photosynthesis and starch accumulation. Manipulating COG1 to optimize photosynthetic capacity would create new strategies for future crop yield improvement.

Receptor-like protein kinases in plant reproduction: Current understanding and future perspectives.

Reproduction is a crucial process in the life span of flowering plants, and directly affects human basic requirements in agriculture, such as grain yield and quality. Typical receptor-like protein kinases (RLKs) are a large family of membrane proteins sensing extracellular signals to regulate plant growth, development, and stress responses. In Arabidopsis thaliana and other plant species, RLK-mediated signaling pathways play essential roles in regulating the reproductive process by sensing different ligand signals. Molecular understanding of the reproductive process is vital from the perspective of controlling male and female fertility. Here, we summarize the roles of RLKs during plant reproduction at the genetic and molecular levels, including RLK-mediated floral organ development, ovule and anther development, and embryogenesis. In addition, the possible molecular regulatory patterns of those RLKs with unrevealed mechanisms during reproductive development are discussed. We also point out the thought-provoking questions raised by the research on these plant RLKs during reproduction for future investigation.

YBX1 Enhances Metastasis and Stemness by Transcriptionally Regulating MUC1 in Lung Adenocarcinoma.

Abnormal expression of the transcription factor Y-box-binding protein-1 (YBX1) is associated with the proliferation, migration, aggressiveness, and stem-like properties of various cancers. These characteristics contribute to the tumorigenesis and metastasis of cancer. We found that the expression levels of Mucin-1 (MUC1) and YBX1 were positively correlated in lung adenocarcinoma cells and lung adenocarcinoma tissue. Our retrospective cohort study of 176 lung adenocarcinoma patients after surgery showed that low expression of both YBX1 and MUC1 was an independent predictor of the prognosis and recurrence of lung adenocarcinoma. In lung adenocarcinoma cells, the silencing/overexpression of YBX1 caused a simultaneous change in MUC1, and MUC1 overexpression partially reversed the decreased tumor cell migration, aggressiveness, and stemness caused by YBX1 silencing. Moreover, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays proved that MUC1 was the downstream target of YBX1 and that YBX1 bound to the -1480~-1476 position in the promoter region of MUC1 to regulate its transcription. Furthermore, in mouse xenograft models and a lung cancer metastasis model, MUC1, which is downstream of YBX1, partially reversed the decreased number and size of tumors caused by YBX1 silencing. In conclusion, our findings indicated a novel mechanism by which YBX1 promotes the stemness and metastasis of lung adenocarcinoma by targeting MUC1 and provided a combination approach for diagnosis different from traditional single tumor biomarkers to predict patient prognosis and provide clinical treatment targets.

Conserved and differentiated functions of CIK receptor kinases in modulating stem cell signaling in Arabidopsis.

The shoot apical meristem (SAM) and root apical meristem (RAM) act as pools of stem cells that give rise to aboveground and underground tissues and organs in higher plants, respectively. The CLAVATA3 (CLV3)-WUSCHEL (WUS) negative-feedback loop acts as a core pathway controlling SAM homeostasis, while CLV3/EMBRYO SURROUNDING REGION (ESR) 40 (CLE40) and WUSCHEL-RELATED HOMEOBOX5 (WOX5), homologs of CLV3 and WUS, direct columella stem cell fate. Moreover, CLV3 INSENSITIVE KINASES (CIKs) have been shown to be essential for maintaining SAM homeostasis, whereas whether they regulate the distal root meristem remains to be elucidated. Here, we report that CIKs are indispensable for transducing the CLE40 signal to maintain homeostasis of the distal root meristem. We found that the cik mutant roots displayed disrupted quiescent center and delayed columella stem cell (CSC) differentiation. Biochemical assays demonstrated that CIKs interact with ARABIDOPSIS CRINKLY4 (ACR4) in a ligand-independent manner and can be phosphorylated by ACR4 in vitro. In addition, the phosphorylation of CIKs can be rapidly induced by CLE40, which partially depends on ACR4. Although CIKs act as conserved and redundant regulators in the SAM and RAM, our results demonstrated that they exhibit differentiated functions in these meristems.

Superconductivity and magnetism in RbEu(Fe1-x Co x )4As4.

We studied the cobalt-doping effect on superconductivity and magnetism in a hole self-doped RbEuFe4As4 magnetic superconductor which shows superconductivity at [Formula: see text] 36.5 K and Eu2+ -spin ordering at [Formula: see text] 15 K. The Co solubility limit in RbEu(Fe1-x Co x )4As4 achieves x = 0.21 for the solid-state reaction at 880 °C. With increasing x, [Formula: see text] decreases gradually, and superconductivity eventually disappears at [Formula: see text]. A spin-density-wave transition at [Formula: see text] 35-40 K is recovered for [Formula: see text], which can be understood in terms of the hole-depletion and the disorder effects. On the other hand, [Formula: see text] remains unchanged despite the Co doping and, consequently, an intriguing superconducting ferromagnet without Meissner state is realized in the range of 0.125 [Formula: see text] 0.155. Our results indicate that the Eu2+ spins essentially decouple with superconductivity over a wide doping range, making the coexistence of superconductivity and ferromagnetism possible in the 1144-type system.

RGF1-RGI1, a Peptide-Receptor Complex, Regulates Arabidopsis Root Meristem Development via a MAPK Signaling Cascade.

Root growth is maintained by the continuous division of cells in the apical meristem. ROOT MERISTEM GROWTH FACTOR 1 (RGF1) is a critical peptide hormone regulating root stem cell niche maintenance. Previous studies discovered that five closely related leucine-rich repeat receptor-like protein kinases (LRR-RLKs), named RGF1 INSENSITIVES (RGIs) or RGF1 RECEPTORS (RGFRs), are able to perceive the RGF1 signal and redundantly control root stem cell niche maintenance. RGF1 regulates root meristem activity mainly via two downstream transcription factors, PLETHORA 1 (PLT1) and PLT2. Regulatory proteins connecting cell surface RGF1-RGI1 and nuclear PLTs, however, were not identified. Here, we report that the mitogen-activated protein (MAP) kinase kinase 4 (MKK4) and MAP kinase 3 (MPK3) were co-immunoprecipitated with RGI1-FLAG after Arabidopsis seedlings were treated with RGF1. Genetic and biochemical assays confirmed that MKK4 and MKK5, and their downstream targets MPK3 and MPK6, are essential RGI-dependent regulators of root meristem development. In addition, we found that the MKK4/MKK5-MPK3/MPK6 module functions downstream of YDA, a MAPKKK. Our results demonstrate that RGF1-RGI1 regulate the expression of PLT1/PLT2 via a YDA-MKK4/MKK5-MPK3/MPK6 signaling cascade.

α1,6-Fucosyltransferase (FUT8) regulates the cancer-promoting capacity of cancer-associated fibroblasts (CAFs) by modifying EGFR core fucosylation (CF) in non-small cell lung cancer (NSCLC).

Cancer-associated fibroblasts (CAFs) are the main cancer-promoting component in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). α1,6-Fucosyltransferase (FUT8), the key enzyme catalyzing core α1,6-fucosylation (CF), plays a promoting role in multiple malignancies. In the current study, we investigated the function of FUT8 in CAFs and elucidated the mechanism through which FUT8 regulates the cancer-promoting capacity of CAFs in NSCLC. A bioinformatics analysis was performed to reveal the relationship between FUT8 and CAFs. Resected specimens from NSCLC patients were analyzed to assess the expression of FUT8 in CAFs. Primary CAFs and normal lung fibroblasts (NLFs) were extracted from NSCLC patient specimens and were co-cultured with NSCLC cell lines in a novel 3D-printed non-contact co-culture device. An In vivo CAF/NSCLC co-injection tumorigenesis assay was performed using nude mice to study the function of FUT8/CF in TME formation. The current study revealed that FUT8-mediated CF in CAFs plays a positive role in the cancer-promoting capacity of these cells. FUT8 overexpression was observed in CAFs isolated from some lung adenocarcinoma cases. Further investigation showed that FUT8/CF in CAFs promoted the formation of an invasive and malignant TME in vivo and in vitro, and the resulting NSCLC cells exhibited faster proliferation and increased invasiveness. EGFR signaling exerts a catalytic effect on the cancer-promoting capacity of CAFs and is regulated by the CF modification of the EGFR protein.

YBX1 mediates autophagy by targeting p110ß and decreasing the sensitivity to cisplatin in NSCLC.

Y-box binding protein 1 (YBX1) is involved in the development of multiple types of tumors. However, the relationship between YBX1 and autophagy in non-small cell lung cancer (NSCLC) remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and markers of autophagy (LC3I/II) in NSCLC and examined their roles in regulating sensitivity to cisplatin in NSCLC. The retrospective analysis of patients with NSCLC indicated that YBX1 was positively correlated with autophagy. Increased levels of YBX1 or autophagy also observed in NSCLC cells compared with those in 16HBE cells. Compared to the controls, the knockdown of YBX1 expression suppressed autophagy, increased drug sensitivity and promoted apoptosis in response to cisplatin in NSCLC cells by targeting the p110ß promoter and inhibiting p110ß/Vps34/beclin1 signaling pathways. We also demonstrated in an in vivo study that the overexpressed YBX1 effectively increased NSCLC growth and progression and decreased the sensitivity to cisplatin by inducing autophagy in a xenograft tumor model, and these effects were concomitant with the increasing of p110ß and beclin1 expression. Collectively, these results show that YBX1 plays an essential role in autophagy in NSCLC.

Effective inhibition of human cytomegalovirus gene expression by DNA-based external guide sequences.

To investigate whether a 12 nucleotide DNA-based miniEGSs can silence the expression of human cytomegalovirus (HCMV) UL49 gene efficiently, A HeLa cell line stably expressing UL49 gene was constructed and the putative miniEGSs (UL49-miniEGSs) were assayed in the stable cell line. Quantitative RT-PCR and western blot results showed a reduction of 67% in UL49 expression level in HeLa cells that were transfected with UL49-miniEGSs. It was significantly different from that of mock and control miniEGSs (TK-miniEGSs) which were 1% and 7%, respectively. To further confirm the gene silence directed by UL49-miniEGSs with human RNase P, a mutant of UL49-miniEGSs was constructed and a modified 5'RACE was carried out. Data showed that the inhibition of UL49 gene expression directed by UL49-miniEGSs was RNase P-dependent and the cleavage of UL49 mRNA by RNase P was site specific. As a result, the length of DNA-based miniEGSs that could silence gene expression efficiently was only 12 nt. That is significantly less than any other oligonucleotide-based method of gene inactivation known so far. MiniEGSs may represent novel gene-targeting agents for the inhibition of viral genes and other human disease related gene expression.

BES1 is activated by EMS1-TPD1-SERK1/2-mediated signaling to control tapetum development in Arabidopsis thaliana.

BES1 and BZR1 were originally identified as two key transcription factors specifically regulating brassinosteroid (BR)-mediated gene expression. They belong to a family consisting of six members, BES1, BZR1, BEH1, BEH2, BEH3, and BEH4. bes1 and bzr1 single mutants do not exhibit any characteristic BR phenotypes, suggesting functional redundancy of these proteins. Here, by generating higher order mutants, we show that a quintuple mutant is male sterile due to defects in tapetum and microsporocyte development in anthers. Our genetic and biochemical analyses demonstrate that BES1 family members also act as downstream transcription factors in the EMS1-TPD1-SERK1/2 pathway. Ectopic expression of both TPD1 and EMS1 in bri1-116, a BR receptor null mutant, leads to the accumulation of non-phosphorylated, active BES1, similar to activation of BES1 by BRI1-BR-BAK1 signaling. These data suggest that two distinctive receptor-like kinase-mediated signaling pathways share BES1 family members as downstream transcription factors to regulate different aspects of plant development.

MicroRNA-30e inhibits proliferation and invasion of non-small cell lung cancer via targeting SOX9.

Previous studies have reported that microRNA-30e (miR-30e) is dysregulated in multiple human cancers. However, the expression, functions and molecular mechanism of miR-30e in NSCLC remain unknown. In this study, we found that miR-30e was expressed at a low level in NSCLC tissues and cell lines. In NSCLC cell lines, enforced expression of miR-30e could inhibit cell proliferation and invasion in vitro. In addition, miR-30e negatively regulated SOX9 expression through directly binding to the 3'UTR of SOX9, and an inverse correlation was found between miR-30e and SOX9 mRNA expression in NSCLC tissues. Moreover, knockdown of SOX9 led to decreased proliferation and invasion of NSCLC cells. Taken together, miR-30e acts as a tumor suppressor in NSCLC, and inhibits cell proliferation and invasion possibly by directly targeting SOX9. These findings might provide novel therapeutic targets for NSCLC.

MACC1 overexpression in carcinoma­associated fibroblasts induces the invasion of lung adenocarcinoma cells via paracrine signaling.

Carcinoma­associated fibroblasts (CAFs) are essential for initiating lung cancer cell invasion and metastasis. An elevated MACC1 expression has been implicated in the progression of lung adenocarcinoma. Hitherto, the role of MACC1 in lung adenocarcinoma­derived CAFs remains unclear. In this study, CAFs isolated from the tissues of patients with lung adenocarcinoma expressed typical CAF markers (shown by immunohistochemical and immunofluorescence analysis) and exhibited enhanced migration and invasion abilities when co­cultured with A549 cells in a microfluidic model. MACC1­overexpressing CAFs not only demonstrated an increased invasion, but also exerted a promoting effect on the invasion of tumor cells. The reduced expression of MACC1 impaired the invasive ability of the CAFs. Western blot analysis and RT­qPCR analysis demonstrated that multiple paracrine pathways were activated in the MACC1­overexpressing CAFs. Overall, this study presents a novel role of MACC1 in CAF­induced lung adenocarcinoma cell invasion, which possibly occurs via paracrine signaling. Furthermore, MACC1 was indicated to be a potential therapeutic target for lung adenocarcinoma.