scholarly journals Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma

2017 ◽  
Author(s):  
E. Mammadova-Bach ◽  
T. Rupp ◽  
C. Spenlé ◽  
I. Jivkov ◽  
P. Shankaranarayanan ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Malignant Tumors ◽  
Tumor Stroma ◽  
Underlying Mechanism ◽  
Gene Signature ◽  
Basement Membranes ◽  
Cancer Targeting ◽  
Anti Cancer ◽  
Low Levels ◽  
Carcinoma Associated Fibroblasts

SummaryTumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumorstroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation. A gene signature comprising LAMA1, ITGB1, ITGA2, CXCR4 and VEGFA has negative predictive value in colon cancer. Together, this information opens novel opportunities for diagnosis and anti-cancer targeting.

scholarly journals Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1346 ◽  
Author(s):  
Naffouje ◽  
Grover ◽  
Yu ◽  
Sendilnathan ◽  
Wolfe ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Cancer Progression ◽  
De Novo ◽  
Malignant Tumors ◽  
Inosine Monophosphate Dehydrogenase ◽  
Variable Response ◽  
Purine Nucleotides ◽  
Proliferating Cells ◽  
Anti Cancer ◽  
Impdh Inhibitors

The purine nucleotides ATP and GTP are essential precursors to DNA and RNA synthesis and fundamental for energy metabolism. Although de novo purine nucleotide biosynthesis is increased in highly proliferating cells, such as malignant tumors, it is not clear if this is merely a secondary manifestation of increased cell proliferation. Suggestive of a direct causative effect includes evidence that, in some cancer types, the rate-limiting enzyme in de novo GTP biosynthesis, inosine monophosphate dehydrogenase (IMPDH), is upregulated and that the IMPDH inhibitor, mycophenolic acid (MPA), possesses anti-tumor activity. However, historically, enthusiasm for employing IMPDH inhibitors in cancer treatment has been mitigated by their adverse effects at high treatment doses and variable response. Recent advances in our understanding of the mechanistic role of IMPDH in tumorigenesis and cancer progression, as well as the development of IMPDH inhibitors with selective actions on GTP synthesis, have prompted a reappraisal of targeting this enzyme for anti-cancer treatment. In this review, we summarize the history of IMPDH inhibitors, the development of new inhibitors as anti-cancer drugs, and future directions and strategies to overcome existing challenges.

scholarly journals MicroRNA-936 Targets JAG1 and Inhibits the Proliferation of Hepatocellular Carcinoma Cells

2021 ◽  
Vol 20 ◽  
pp. 153303382098578
Author(s):  
Junmei Tian ◽  
Yongfei Zhao ◽  
Li Li ◽  
Yanling Cui ◽  
Yang Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cancer Progression ◽  
Malignant Tumors ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Functional Study ◽  
Functional Roles ◽  
Anti Cancer ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Investigating the underlying molecular mechanism is essential for the treatment and prognosis of HCC. Emerging evidence suggests that microRNAs (miRNAs) play pivotal roles in cancer progression. Down-regulation of miR-936 has been found in several cancers, which serves as a tumor suppressor to inhibit the development of cancers. However, the clinical significance and functional roles of miR-936 in HCC have not been determined. To explore this, the expression of miR-936 in HCC tissues and cells was detected by RT-qPCR. Cell Counting Kit-8 (CCK-8) assay, cell migration and cell cycle analysis were performed to evaluate the effects of miR-936 on the growth of HCC cells. The targets of miR-936 were predicted using the miRDB database and confirmed by luciferase reporter experiments. The protein expression of targets was determined by western blot. The results showed that miR-936 was significantly decreased in HCC tissues and cell lines. Low expression of miR-936 was associated with the advance progression and poor survival of HCC patients (P = 0.0036). Functional study revealed that overexpression of miR-936 inhibited the proliferation, migration (decreased to ∼0.26 fold) and induced cell cycle arrested in G1 phase (from 35.3% to 44.7%) of HCC cells. Additionally, miR-936 targeted the 3′-untranslated region (UTR) of jagged-1 (JAG1) and reduced the expression of JAG1 (decreased to ∼0.35 fold). JAG1 was found to be up-regulated in HCC tissues and was inversely correlated with the expression of miR-936 (Pearson r = −0.4633; P = 0.0007). The anti-cancer effects of miR-936 on the proliferation of HCC cells were partially reversed by the rescue of JAG1. Therefore, these results suggested that miR-936 might be a potential target for HCC treatment.

scholarly journals Gene signature characteristic of elevated stromal infiltration and activation is associated with increased risk of hematogenous and lymphatic metastasis in serous ovarian cancer

2019 ◽  
Author(s):  
Huiran Yue ◽  
Jieyu Wang ◽  
Ruifang Chen ◽  
Xiaoman Hou ◽  
Jun Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Lymphatic Metastasis ◽  
Distant Metastases ◽  
Tumor Stroma ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Primary Tumors ◽  
Tumor Invasiveness ◽  
Increased Risk

Abstract Background The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer.Methods Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases.Results We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer.Conclusions Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

Elaborating the Role of Natural Products on the Regulation of Autophagy and their Potentials in Breast Cancer Therapy

2018 ◽  
Vol 18 (3) ◽  
pp. 239-255 ◽  
Author(s):  
Xunian Zhou ◽  
Grace Gar-Lee Yue ◽  
Stephen Kwok-Wing Tsui ◽  
Jianxin Pu ◽  
Kwok-Pui Fung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Natural Products ◽  
Malignant Tumors ◽  
Underlying Mechanism ◽  
Lysosomal Hydrolases ◽  
Potential Implication ◽  
Growth And Survival ◽  
Protein Levels ◽  
Cancer Breast ◽  
Anti Cancer

Autophagy is an intracellular lysosomal/vacuolar degradation system, in which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. However, disturbance in the autophagic process is often associated with a variety of human diseases, such as cancer. Breast cancer is one of the most malignant tumors characterized by the imbalanced cell proliferation, apoptosis as well as disordered autophagy regulation. The alterations of autophagy related genes or protein levels in breast cancer cells also suggested a potential implication of autophagy in breast cancer development and progression. Many natural products had been reported as potential anti-cancer agents or being considered as direct or indirect sources of new chemotherapy adjuvants to enhance the efficacy or to ameliorate the side effects through the modulation of autophagy. Investigation of the underlying mechanism of these compounds could be crucial for the development of new therapeutic or chemopreventive options for breast cancer treatment. In this review, a summary of those natural products that can regulate autophagy in breast cancer is presented and the potential value of such autophagy modulators on the development of anti-cancer drugs is also discussed.

scholarly journals Gene signature characteristic of elevated stromal infiltration and activation is associated with increased risk of hematogenous and lymphatic metastasis in serous ovarian cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Huiran Yue ◽  
Jieyu Wang ◽  
Ruifang Chen ◽  
Xiaoman Hou ◽  
Jun Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Lymphatic Metastasis ◽  
Distant Metastases ◽  
Tumor Stroma ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Serous Ovarian Cancer ◽  
Primary Tumors ◽  
Increased Risk

Abstract Background The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer. Methods Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases. Results We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer. Conclusions Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

scholarly journals Gene signature characteristic of elevated stromal infiltration and activation is associated with increased risk of hematogenous and lymphatic metastasis in serous ovarian cancer

2019 ◽  
Author(s):  
Huiran Yue ◽  
Jieyu Wang ◽  
Ruifang Chen ◽  
Xiaoman Hou ◽  
Jun Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Lymphatic Metastasis ◽  
Distant Metastases ◽  
Tumor Stroma ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Primary Tumors ◽  
Tumor Invasiveness ◽  
Increased Risk

Abstract Background The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer.Methods Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases.Results We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer.Conclusions Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

Recent Advances in the Function of the 67 kDa Laminin Receptor and its Targeting for Personalized Therapy in Cancer

2017 ◽  
Vol 23 (32) ◽  
pp. 4745-4757 ◽  
Author(s):  
Ada Pesapane ◽  
Pia Ragno ◽  
Carmine Selleri ◽  
Nunzia Montuori
Keyword(s):  
Cell Adhesion ◽  
Cancer Progression ◽  
Ribosome Biogenesis ◽  
Critical Role ◽  
Protein Translation ◽  
Basement Membranes ◽  
Laminin Receptor ◽  
Cell Surface Receptor ◽  
Future Application ◽  
Neoplastic Cells

The 67 kDa high affinity laminin receptor (67LR) is a non-integrin cell surface receptor for laminin, the major component of basement membranes. Interactions between 67LR and laminin play a major role in mediating cell adhesion, migration, proliferation and survival. 67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), most probably by fatty acid acylation. Interestingly, 37LRP, also called p40 or OFA/iLR (oncofetal antigen/immature laminin receptor), is a multifunctional protein with a dual activity in the cytoplasm and in the nucleus. In the cytoplasm, 37LRP it is associated with the 40S subunit of ribosome, playing a critical role in protein translation and ribosome biogenesis while in the nucleus it is tightly associated with nuclear structures, and bound to components of the cytoskeleton, such as tubulin and actin. 67LR is mainly localized in the cell membrane, concentrated in lipid rafts. Acting as a receptor for laminin is not the only function of 67LR; indeed, it also acts as a receptor for viruses, bacteria and prions. 67LR expression is increased in neoplastic cells and correlates with an enhanced invasive and metastatic potential. The primary function of 67LR in cancer is to promote tumor cell adhesion to basement membranes, the first step in the invasion-metastasis cascade. Thus, 67LR is overexpressed in neoplastic cells as compared to their normal counterparts and its overexpression is considered a molecular marker of metastatic aggressiveness in cancer of many tissues, including breast, lung, ovary, prostate, stomach, thyroid and also in leukemia and lymphoma. Thus, inhibiting 67LR binding to laminin could be a feasible approach to block cancer progression. Here, we review the current understanding of the structure and function of this molecule, highlighting its role in cancer invasion and metastasis and reviewing the various therapeutic options targeting this receptor that could have a promising future application.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

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