Stretching of the Skin In Vivo. A Method of Influencing Cell Division and Migration in the Rat Epidermis**From the Departments of Physiology and Biophysics and of Oral Surgery, Georgetown University Schools of Dentistry and Medicine, Washington, D. C.

Cancer is one of the most prevalent and deadly diseases in today's society, affecting millions of people around the globe. Uncontrolled cell division and migration which are two of the six major hallmarks of cancer have been studied extensively in vitro, however in vivo these hallmarks are not well understood. We used the Caenorhabditis elegans nematode worm as our model organism in order to study these two hallmarks. In unfavorable environmental conditions such as starvation, C. elegans can enter a developmental arrest in where certain cell metabolism ceases to continue, this stage is known as L1 arrest. Normally in L1 arrested worms, there are 2 distinct Q neuroblast cells which are precursors of sensory and interneurons that do not divide and migrate. However, when we mutate certain genes, we noticed that the two Q neuroblasts inappropriately divided and migrated, this suggests that we have identified a good model to study uncontrolled cell division and migration. We have already found one gene that when mutated, results in the Q neuroblasts inappropriately dividing and migrating at L1 arrest, now we are looking for other mutated genes that can cause this phenotype, this ultimately allows us to identify new mechanisms that cause an increase risk in cancer.

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Targeting Matrix Metalloproteinases in Atherosclerosis and Cardiovascular Dysfunction

Revista de Chimie ◽

10.37358/rc.19.2.6992 ◽

2019 ◽

Vol 70 (2) ◽

pp. 718-720

Author(s):

Lucia Corina Dima-Cozma ◽

Sebastian Cozma ◽

Delia Hinganu ◽

Cristina Mihaela Ghiciuc ◽

Florin Mitu

Keyword(s):

Smooth Muscle ◽

Matrix Metalloproteinases ◽

Cholesterol Synthesis ◽

Balloon Dilation ◽

Aortic Aneurysms ◽

Arterial Lesions ◽

Smooth Muscle Cell Migration ◽

And Migration

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.

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Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

Cell Death and Disease ◽

10.1038/s41419-021-03664-1 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jianye Xu ◽

Jian Zhang ◽

Zongpu Zhang ◽

Zijie Gao ◽

Yanhua Qi ◽

...

Keyword(s):

Macrophage Polarization ◽

Autophagy Induction ◽

Antitumor Immunotherapy ◽

Novel Biomarkers ◽

And Migration ◽

Immunosuppressive Microenvironment ◽

Proliferation And Migration ◽

Glioma Progression

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

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The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-90220-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yu Zhang ◽

Zhaohui Zhong ◽

Mei Li ◽

Jingyi Chen ◽

Tingru Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Significance ◽

Growth Factor Receptor ◽

The Cancer Genome Atlas ◽

Actin Dynamics ◽

Elevated Expression ◽

Sw480 Cells ◽

And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

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Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa108 ◽

2020 ◽

Author(s):

Yuanyuan Wang ◽

Shanqi Guo ◽

Yingjie Jia ◽

Xiaoyu Yu ◽

Ruiyu Mou ◽

...

Keyword(s):

Prostate Cancer ◽

Flavonoid Compound ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

Invasion And Migration ◽

Beneficial Effects ◽

Anticancer Properties ◽

Xenograft Models ◽

And Migration

ABSTRACT Prostate cancer (PCa) is one of the important factors of cancer deaths especially in the western countries. Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) is a phenolic flavonoid compound proved to possess anticancer properties, but its effects on PCa are left to be released. The aims of this study were to investigate the effects and the relative mechanisms of Hispidulin on PCa development. Hispidulin administration inhibited proliferation, invasion, and migration, while accelerated apoptosis in Du145 and VCaP cells, which was accompanied by PPARγ activation and autophagy enhancement. The beneficial effects of Hispidulin could be diminished by PPARγ inhibition. Besides, Hispidulin administration suppressed PCa tumorigenicity in Xenograft models, indicating the anticancer properties in vivo. Therefore, our work revealed that the anticancer properties of Hispidulin might be conferred by its activation on PPARγ and autophagy.

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Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

BMC Molecular and Cell Biology ◽

10.1186/s12860-021-00360-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhenghui Cheng ◽

Yawen Zhang ◽

Yinchao Tian ◽

Yuhan Chen ◽

Fei Ding ◽

...

Keyword(s):

Nerve Injury ◽

Peripheral Nerves ◽

Molecular Mechanisms ◽

Αvβ3 Integrin ◽

Promoting Effect ◽

Ccn Family ◽

And Migration ◽

Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

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Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

Cytogenetic and Genome Research ◽

10.1159/000512264 ◽

2020 ◽

Vol 160 (11-12) ◽

pp. 650-658

Author(s):

Yichen Le ◽

Yi He ◽

Meirong Bai ◽

Ying Wang ◽

Jiaxue Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Cancer Progression ◽

Normal Liver ◽

Cell Growth And Migration ◽

And Migration ◽

Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

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Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22041985 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1985

Author(s):

Xiaohe Li ◽

Ling Ma ◽

Kai Huang ◽

Yuli Wei ◽

Shida Long ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Kinase Inhibitor ◽

In Vivo Experiments ◽

Age Related ◽

And Migration ◽

Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

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Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211027898 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110278

Author(s):

Yayan Yang ◽

Qian Feng ◽

Chuanfeng Ding ◽

Wei Kang ◽

Xiufeng Xiao ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Click Reaction ◽

Chemotherapy Drugs ◽

Targeting Peptide ◽

And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

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Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma

Cancer Cell International ◽

10.1186/s12935-021-01796-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

JiangSheng Zhao ◽

GuoFeng Chen ◽

Jingqi Li ◽

Shiqi Liu ◽

Quan Jin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle Progression ◽

Lung Metastases ◽

Cell Counting ◽

Migration And Invasion ◽

Signal Pathways ◽

And Migration ◽

Healthy Liver

Abstract Background PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. Methods PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. Results PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. Conclusions This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.

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