Endolymphatic sac tumor misdiagnosed as metastatic renal cell carcinoma: Pitfalls in morphology and immunohistochemistry.

Endolymphatic sac tumor (ELST) is a rare disease that originates from the endolymphatic sac system of the inner ear. Being a low-grade malignant tumor, ELST has a mild morphology and is characterized by a slow but aggressive growth. Most clinicians and pathologists are unfamiliar with this disease. ELST can be misdiagnosed as metastatic renal cancer because of the similarity in morphology and expression of nephrogenic markers such as PAX8. The presented case of a 27-year-old man revealed that observing the characteristic location and confirming the absence of renal neoplasm to rule out the possibility of metastasis are critical for obtaining an accurate final diagnosis.

Hsa_circ_0007707 participates in PDE3B-mediated apoptosis inhibition and inflammation promotion in fibroblast-like synoviocytes.

Synovial samples collected from 30 rheumatoid arthritis (RA) patients and 30 normal controls were used to isolate fibroblast-like synoviocytes (FLSs) and named FLS-RA and FLS-Normal, respectively. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to detect circ_0007707 expression. Effects of circ_0007707 silencing on cell proliferation and apoptosis were evaluated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine (Edu), and flow cytometry assays. Levels of pro-inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Increased circ_0007707 expression was observed in synovial samples from RA patients and FLS-RA cells. Functional analysis showed circ_0007707 silencing restrained cell proliferation, induced cell apoptosis, and decreased cell inflammatory response in FLS-RA cells. Mechanistic analysis revealed the sponge function of circ_0007707 on miR-27b-3p, and miR-27b-3p inhibition weakened circ_0007707 knockdown-mediated effects on FLS-RA cell proliferation, apoptosis, and inflammatory response. Circ_0007707 could mediate PDE3B expression via sponging miR-27b-3p, and PDE3B overturned miR-27b-3p mimic-mediated effects on FLS-RA cell proliferation, apoptosis, and inflammatory response. Circ_0007707 mediated cell apoptosis and inflammatory response in FLS-RA cells through the miR-27b-3p/PDE3B axis, indicating the potential function of circ_0007707 as a target for RA treatment.

Single-port thoracoscopic resection of a posterior mediastinal Mullerian cyst in a woman.

Mullerian cysts are benign tumors that are very rare in the posterior mediastinum. It is necessary to distinguish Mullerian cysts from benign tumors or other types of cyst in the posterior mediastinum. A 42-year-old woman visited our hospital for a routine check-up, and a mediastinal mass was identified on chest computed tomography (CT). Contrast-enhanced chest magnetic resonance imaging (MRI) revealed a 4.0 × 2.6 × 2.8-cm mass, and a neurogenic tumor or esophageal cyst was suspected. Single-port thoracoscopic surgery was performed for cyst removal. Histopathological examination of the resected tissue revealed that the cyst wall was covered with a single layer of ciliated columnar epithelium. Immunohistochemical staining revealed positivity for paired box gene 8 (PAX8), Wilms tumor protein 1 (WT-1), estrogen receptor (ER), and progesterone receptor (PR). Therefore, a diagnosis of mediastinal Mullerian cyst was made. Mediastinal Mullerian cysts should be included in the differential diagnosis of posterior mediastinal cysts. Cystic lesions in the posterior mediastinum should be removed surgically and undergo immunohistochemical examination.

CHRAC1 promotes human lung cancer growth through regulating YAP transcriptional activity.

ATP-dependent chromatin remodeling complexes regulate chromatin structure and play important roles in gene expression, differentiation, development and cancer progression. Dysregulation in the subunits of the complexes often has been found in different cancers, but how they influence cancer initiation and progression is not fully understood. Here, we show that Chromatin Accessibility Complex Subunit 1 (CHRAC1), the accessory subunit of chromatin remodeling complex, is highly expressed in lung cancer tissues, which correlates with poor prognosis in lung cancer patients. CHRAC1 overexpression promotes lung cancer cell proliferation and migration in vitro and tumor growth in genetically engineered KrasG12D.LSL lung adenocarcinoma mouse model. Consistent with this, CHRAC1 silencing inhibits cell proliferation and migration in lung cancer cells and suppresses tumor growth in xenograft mouse model. Further, CHRAC1 binds to the transcription coactivator Yes-associated protein (YAP), enhances the transcription of downstream target oncogenes in Hippo pathway and thus promotes the tumor growth. Together, our study defines a critical role of CHRAC1 in promoting YAP transcriptional activity and lung cancer tumorigenesis, which makes it a potential target for lung cancer.

MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING.

Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 patients with lung cancer under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progression-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T-cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20,000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted natural killer (NK) cells and decreased CD8+ T-cell and NK-cell populations in patients with MET amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3'-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET. SIGNIFICANCE: We suggest that the combination of MET inhibitor together with ICB will overcome ICB resistance induced by MET amplification. Our report reveals much-needed information that will benefit the treatment of patients with primary MET amplification or EGFR-tyrosine kinase inhibitor resistant-related MET amplification.This article is highlighted in the In This Issue feature, p. 2659.

Muir-Torre Syndrome With a Frame-shift Mutation in the MSH2 Gene: A Rare Case Report and Literature Review.

Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syndrome. NexGen sequencing identified a frame-shift mutation in the MSH2 gene. The patient was found to have a metachronous colorectal carcinoma, uterine endometrial carcinoma, and skin cancer from 1998 to 2016. Five family members had also suffered from colorectal cancer or glioma. This case report illustrates the importance of the multidisciplinary care approach, mismatch repair protein and gene testing, and detailed medical history taking into consideration the diagnosis of Muir-Torre syndrome.

Plasma-Assisted Surface Modification on the Electrode Interface for Flexible Fiber-Shaped Zn-Polyaniline Batteries.

A novel flexible fiber-shaped zinc-polyaniline battery (FZPB) is proposed to enhance the electrochemical performance, mass loading, and stability of polyaniline cathodes. To this end, electron-cyclotron-resonance oxygen plasma-modified carbon fibers are employed. During plasma treatment, on the carbon-fiber surface, O2+ plasma breaks the C-C, C-H, and C-N bonds to form C radicals, while the O2 molecules are broken down to reactive oxygen species (O+, O2+, O2+, and O22+). The C radicals and the reactive oxygen species are combined to homogeneously form oxygen functional groups, such as -OH, -COOH, and -C═O. The surface area and total pore volume of the treated carbon fibers increase as the plasma attacks. During electrodeposition, aniline interacts with the oxygen functional groups to form N-O and N-H bonds and π-π stacking, resulting in a homogeneous and high-loading polyaniline structure and improved adhesion between polyaniline and carbon fibers. In an FZPB, the cathode with plasma-treated carbon fibers and a polyaniline loading of 0.158 mg mgCF-1 (i.e., 2.36 mg cmCF-1) exhibits a capacity retention of 95.39% after 200 cycles at 100 mA g-1 and a discharge capacity of 83.96 mA h g-1 at such a high current density of 2000 mA g-1, which are ∼1.67 and 1.24 times those of the pristine carbon-fiber-based one, respectively. Furthermore, the FZPB exhibits high flexibility with a capacity retention of 86.4% after bending to a radius of 2.5 mm for 100 cycles as a wearable energy device.

Lobar location of lesions in computed tomography-guided lung biopsy is correlated with major pneumothorax: A STROBE-compliant retrospective study with 1452 cases.

Pneumothorax is a common complication in computed tomography (CT)-guided percutaneous lung biopsy (CPLB). Whether the lobar location of lesions contributes to the incidence of pneumothorax should be further clarified.A total of 1452 consecutive patients who underwent CPLB between January 2010 and March 2018 were retrospectively analyzed. The incidence of pneumothorax was compared among 5 different lobe biopsies. Minor pneumothorax was defined as pneumothorax without chest tube placement and major pneumothorax was defined as pneumothorax with chest tube placement.The positive diagnosis rate of pathology for this cohort was approximately 84%, with 22.5% (326/1452) of the patients experiencing pneumothorax. The rates of pneumothorax were 19.5%, 24.5%, 33.9%, 21.4%, and 23.9% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe, respectively (P = .09). Chest tube placement was necessary in 19.0% (62/326) of the patients with pneumothorax. The rates of major pneumothorax were 5.3%, 2.6%, 10.2%, 4.7%, and 2.6% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe biopsies, respectively (P = .02). This result was further confirmed by the propensity score-matching method. Moreover, 8.7% (127/1452) of the patients experienced puncture of fissure, the rates of which were 13.5%, 5%, 10.2%, 9.1%, and 4.3% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe, respectively (P < .001). Within the pneumothorax patient group, the rate of lobe fissure puncture (15.2%) was significantly lower in patients with minor pneumothorax than (51.6%) in those with major pneumothorax (P < .001).Upper and middle lobe lesion biopsies show a significantly high rate of major pneumothorax, which may be due to more puncture of fissure. It is crucial to carefully distinguish the fissure around lesions and bypass it to avoid major pneumothorax.

Performance evaluation of interfacial polymerisation-fabricated aquaporin-based biomimetic membranes in forward osmosis.

Aquaporins play a promising role in the fabrication of high-performance biomimetic membranes. Interfacial polymerisation is a promising strategy for synthesizing aquaporin-based membranes. In this study, robust and high-performance aquaporin-based biomimetic membranes were successfully fabricated by interfacial polymerisation, and the membrane separation performance and interfacial polymerisation method were systematically evaluated. The effects of modification methods on the performance of aquaporins-based biomimetic membranes, including sodium hypochlorite and thermal post-treatment, protein-to-lipid ratio, liposome concentration and the addition arrangement of aquaporins were also investigated. Morphological observation suggested that the introduced proteoliposomes were completely embedded in the polyamide layer and that their spherical shape was preserved. Sodium hypochlorite post-treatment and thermal treatment were beneficial in improving the water flux and salt rejection of the resultant membrane without sacrificing the aquaporin activity. The biomimetic membranes had a high water flux and salt rejection, which were almost twice that of the control membranes, after aquaporin-based proteoliposomes were incorporated with an appropriated protein-to-lipid ratio and liposome concentration. The addition arrangement of aquaporins during the interfacial polymerisation procedure significantly influence the obtained membrane's structure. Lastly, this article introduces valuable and systematic research on interfacial polymerisation fabricated aquaporin-based biomimetic membranes with outstanding separation performance.

Correction: Performance evaluation of interfacial polymerisation-fabricated aquaporin-based biomimetic membranes in forward osmosis.

[This corrects the article DOI: 10.1039/C9RA00787C.].

Expansile invasive growth pattern is definite evidence for the diagnosis of small hepatocellular carcinomas: a comparative study of 37 cases.

Small HCCs, including seHCC and spHCC, are rarely encountered in daily practice. Definite diagnosis is difficult for general pathologists. In this study, we reviewed 1025 cases of HCC and examined the histologic characteristics of small HCCs to facilitate more accurate diagnosis. Slides of archived HCC cases were reviewed by 2 senior pathologists, and small HCCs were identified according to the canonical criteria. Additional immunohistochemical stains were performed. Thirty-seven cases of small HCC were identified, including 22 cases of seHCC and 15 cases of spHCC. We found 2 types of invasive growth patterns in these lesions. The first is the expansile invasive growth pattern, with monomorphic tumor cells penetrating through the incomplete fibrous capsules and expanding into the adjacent noncancerous liver with a spherical, hemispheric, or mushroom shape. The second is the classic stromal invasion pattern. At least one type of invasive pattern was observed in all of the 37 cases of small HCC, and the seHCCs exhibit the expansile invasive growth pattern more frequently than the classic stromal invasion pattern. On the contrary, stromal invasive pattern was more common in spHCC nodules. In conclusion, with the background of chronic hepatitis and cirrhosis, histologic features including crowdedness of hepatocytic trabeculae and the expansile invasive growth pattern are strong evidence for the diagnoses of small HCC.

ZnO Nanorod Array Modified PVDF Membrane with Superhydrophobic Surface for Vacuum Membrane Distillation Application.

The vacuum membrane distillation (VMD) is a promising technology for lots of applications. To solve the membrane fouling and wetting problems, in this paper, a novel ZnO nanorods 1 H,1 H,2 H,2 H-perfluorodecyltriethoxysilane (PDTS) modified poly(vinylidene fluoride) (PVDF) membrane with a micro/nanoscale hierarchical structure and a superhydrophobic surface has been prepared and applied to the VMD process for distilling highly salty water, for the first time. Among these, a pyrolysis-adhesion method is created to obtain the ZnO seeds and fasten them on the PVDF substrate firmly. The novel modified membrane shows a stable superhydrophobic surface with a water contact angle of 152°, easy cleaning property, excellent thermal and mechanical stability, because of the Cassie's state caused by pocketing much air in the hydrophobized ZnO nanorods, the low surface energy of PDTS coating, and the strong adhesion between ZnO nanorods and PVDF membrane, which has built an ideal structure for VMD application. After 8 h VMD of 200 g L-1 NaCl solution, compared to the virgin PVDF membrane, the novel membrane shows a similar permeate flux but a much higher quality permeated liquid because of its unique antifouling and antiwetting caused by the several microns gap between the feed and the membrane. Due to its easy cleaning property, the novel membrane also exhibits an excellent reusability.

Metastatic spread of solid subtype lung adenocarcinoma to the small intestine with anemia and melena: A case report.

RATIONALE: Metastasis to the small intestine from a primary lung cancer is rare, and is associated with a poor prognosis. Early diagnosis of small intestine metastasis is difficult because of the low incidence of clinically apparent symptoms. PATIENT CONCERNS: Clinical data and treatment of a 59-year-old man with small intestine metastasis from primary solid subtype lung adenocarcinoma are summarized. DIAGNOSES: A man who was previously diagnosed with stage IIIA (T3N2M0) lung adenocarcinoma (solid subtype) came to our hospital for postoperative radiotherapy. Laboratory tests indicated anemia and melena. The patient was initially believed to have digestive ulcer and was treated with omeprazole, which proved to be ineffective. We conducted an abdominal computed tomography (CT) contrast scan and discovered a mass in the small intestine mass. Further positron emission tomography-computed tomography (PET-CT) imaging indicated the small intestine mass with fluorodeoxyglucose uptake. INTERVENTIONS: The patient underwent an enterectomy and anastomosis. Pathological analysis confirmed the diagnosis of small intestinal metastasis from lung cancer with concomitant mesenteric lymph node metastasis. OUTCOMES: One month after the operation, hemoglobin levels became normal, and the patient had good quality of life. However, 3 months after the operation, the patient suffered from anemia again. An abdominal CT scan indicated a new small intestine mass. Progression continued rapidly, and the patient died of hemorrhagic shock 5.5 months after the resection of the small intestine mass. LESSONS: Although uncommon, if lung cancer patients present with anemia and melena, enteric metastasis should be part of the differential diagnosis. Abdominal CT scans and PET-CT are effective for early diagnosis. The prognosis of metastatic spread of solid subtype lung adenocarcinoma to the small intestine with mesenteric lymph node metastasis is poor. Subgroups of patients benefitting from metastasectomy and more effective systemic therapy need to be further investigated.

Immunohistochemistry as a quick screening method for clinical detection of BRAF(V600E) mutation in melanoma patients.

With the increased uses of targeted therapeutics, diagnostic detection of target mutations becomes essential for the effective clinical applications of targeted therapeutics. Currently, there are two types of methods detecting target mutations in clinics: one is based on DNA sequence and the other uses the newly developed mutation-specific antibodies recognizing mutated proteins. Each method has its own advantages and disadvantages. Here, we explored the sensitivity and specificity of a new commercially available BRAF(V600E) mutation-specific mouse monoclonal antibody. Using routine manual immunohistochemistry (IHC), we tested tumor tissues from 38 melanoma patients. For those melanoma tissues with abundant endogenous melanin, we pretreated the tumor tissues with 3 % hydrogen peroxide to remove melanin for reliable signal detection. We also performed DNA sequencing and ARMS-PCR analyses for these 38 tumor samples. Comparing to the results from DNA-based detection methods, the IHC method with this BRAF(V600E) mutation-specific antibody displayed 100 % sensitivity and 92.9 % specificity. Hence, this IHC detection is sensitive for clinic uses as a simple, fast, inexpensive, and reliable method to screen cancer patients for the BRAF(V600E) mutation and could be easily adapted for use in most hospital pathology laboratories.

Bis(tetra-butyl-ammonium) [2-(eth-oxy-carbony)phenyl-imido]-µ(6)-oxido-dodeca-µ(2)-oxido-penta-oxidohexa-molybdenum diethyl ether hemisolvate.

In the title complex, [(C(4)H(9))(4)N](2)[Mo(6)O(18)(C(9)H(9)NO(2))]·0.5C(4)H(10)O, the aryl-imido ligand is linked to an Mo atom of the Lindqvist-type polyoxidometalate anion by an Mo N bond of 1.726 (4) Å. The Mo N-C angles are 160.7 (5) and 167.6(5)° because of disorder affecting the aryl group, and is typical for the imido monodentate behaviour described in analogous hybrids. Light components of the structure are extensively disordered. The aryl ester group is disordered over two positions with occupancies refined to 0.559 (3) and 0.441 (3). Both independent tetra-butyl-ammonium cations have butyl chains partially split over two sites, with occupancies as in the aryl group of the anion. Finally, the ether solvent mol-ecule is disordered around an inversion centre. In the crystal, cations and anions inter-act via C-H⋯O contacts, involving O atoms of the polyoxidometalate anion and the ester group of the aryl-imido ligand as acceptor groups.

Involvement of p120 in LPS-induced NF-kappaB activation and IL-8 production in human bronchial epithelial cells.

P120-catenin (p120), a prototypic member of a subfamily of Armadillo repeat domain (Arm domain) proteins, not only participates in cell-cell adhesion, but also mediates inflammatory responses in the skin. In the present study, we demonstrated the effect of p120 on lipopolysaccharide (LPS)-induced inflammatory responses in human bronchial epithelial cells (BECs). We first confirmed that p120 expression was significantly reduced after LPS stimulation in BECs, the p65 subunit of nuclear factor-kappaB (NF-kappaB) nuclear translocation was promoted and NF-kappaB activity was rapidly induced. Moreover, the expression level of interleukin-8 (IL-8) increased after LPS treatment. Over-expression of p120 attenuated LPS-stimulated NF-kappaB reporter gene expression and IL-8 mRNA expression and protein synthesis. On the contrary, transfection with p120 small interfering RNA (siRNA) significantly elevated LPS-stimulated NF-kappaB transcriptional activity, p65 nuclear translocation and IL-8 expression. Collectively, these results indicate an anti-inflammatory effect of p120 in BECs, through its modulation of NF-kappaB signaling.

Bleomycin-induced nuclear factor-kappaB activation in human bronchial epithelial cells involves the phosphorylation of glycogen synthase kinase 3beta.

Nuclear factor-kappaB (NF-kappaB) plays a central role in the development of bleomycin (BLM) lung toxicity, but the regulatory mechanisms are still unknown. In the present study, we investigated the cytotoxic effect of BLM on cultured human bronchial epithelial cells (BECs) and first confirmed that BLM induced the transcriptional activation of NF-kappaB signaling in BECs. We also found that BLM activated Akt (protein kinase B, PKB) and increased the phosphorylation level of glycogen synthase kinase 3beta (GSK3beta). GSK3beta is known to be a key downstream target of Akt, and LY294002, the PI3K (phosphatidylinositol 3-kinase)/Akt inhibitor, which promoted the dephosphorylation of GSK3beta, significantly attenuated BLM-induced NF-kappaB activation. Next, we further observed that constitutively active GSK3beta stabilized the inhibitor of NF-kappaB (IkappaBalpha), inhibited p65 nuclear translocation and partially blocked BLM-induced NF-kappaB activation. Importantly, a co-immunoprecipitation assay revealed that GSK3beta formed a complex with IkappaBalpha, while GSK3beta phosphorylation caused by BLM led to their dissociation. These results suggest that BLM can induce the activation of NF-kappaB signaling in BECs and this process is tightly associated with the phosphorylation status of GSK3beta, implying a possible regulatory mechanism of NF-kappaB signaling in BECs during the toxic lung injury induced by BLM.

Glycogen synthase kinase 3beta induces apoptosis in cancer cells through increase of survivin nuclear localization.

Glycogen synthase kinase 3beta (GSK3beta) regulates numerous signaling pathways that control a wide range of cellular processes, including cell proliferation, differentiation, apoptosis and metabolism. We report a novel function of GSK3beta: It interacts with the inhibitor-of-apoptosis protein (IAP) survivin to modulate its expression, thus regulating apoptosis in human lung cancer cells. A co-immunoprecipitation assay revealed that GSK3beta can bind survivin. Activation of GSK3beta induced translocation of survivin from the cytoplasm to the nucleus, resulting in G1 cell-cycle arrest and apoptosis, as well as sensitization to the chemotherapeutic drug doxorubicin. In contrast, inactivation of GSK3beta, either by transfection of a dominant-negative mutant inhibitor DN-GSK3beta or with selective inhibitor LiCl, increased cytoplasmic survivin expression, leading to cell-cycle progression and resistance to apoptosis. These results identify a pro-apoptotic role for GSK3beta in cancer cells, through its modulation of survivin in subcellular redistribution. This new role suggests that there is a potential for pharmacologic activation of GSK3beta to enhance treatment of cancer patients, including those with resistance.

IQ domain GTPase-activating protein 1 mediates the process of injury and repair in bronchial epithelial cells.

The process of injury and repair in airway epithelium involves cell spreading and migration followed by cell proliferation. IQ domain GTPase-activating protein 1 (IQGAP1) acts in a series of cell processes, but has not been clarified in lung epithelial cells. In this study, a widely used model of injury and repair in vitro by scratching bronchial epithelial cells (BECs) was utilized to investigate the function of IQGAP1. The results showed that IQGAP1 was abundant in BECs of mouse, rat, pig and human. IQGAP1 was colocalized with tubulin cytoskeleton, but was destroyed by nocodazole, a microtubule disassembly reagent. IQGAP1 mRNA and protein expressions increased at 6-9 h after scratching. In addition, overexpression of IQGAP1 translocated ß-catenin from the cytoplasm into the nucleus and activated the Tcf/Lef signal. Scratching altered the associations of IQGAP1 with ß-catenin, adenomatous polyposis coli (APC) and cytoplasmic linker protein-170 (CLIP-170). Silencing IQGAP1 expression by small interference RNA (siRNA) blocked the wound closure. It is concluded that IQGAP1 signal is involved in the wound closure of BECs induced by scratching.

IQGAP1 promotes cell proliferation and is involved in a phosphorylation-dependent manner in wound closure of bronchial epithelial cells.

The re-epithelialization process of the airway involves spreading and migration followed by cell proliferation. Scaffold IQ domain GTPase-activating protein (IQGAP1), an effector of Rho GTPases, is a key component in a series of cell processes, although its exact mechanism in injury and repair of the airway is still unclear. In this study, we utilized a widely used model in vitro by scratching bronchial epithelial cells (BECs). At different time points after scratching, the amounts of IQGAP1 in mRNA and protein were greater than that in the control. PKCepsilon-mediated phosphorylation of IQGAP1 was involved in the process of injury and repair. The overexpression of PKCepsilon or treatment with phorbol-12-myristate-13-acetate (the PKC activator) promoted wound closure. On the contrary, the group treated with GF109203X (the PKC inhibitor) had the opposite effect. Scratching or overexpression of IQGAP1 induced increasing amounts of total beta-catenin and the transposition of beta-catenin from the cytoplasm into the nucleus. These results activated the T cell factor/lymphoid enhanced factor and induced expression levels of its target genes of c-myc and cyclin D1. The reduction of IQGAP1 by the transfection of small interference RNA of IQGAP1 attenuated these effects and directly impaired the scratching-induced wound closure. Taken together, our results suggest that IQGAP1 promotes cell proliferation and phosphorylation of IQGAP1 is involved in the process of wound closure in BECs.