scholarly journals Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

2018 ◽  
Vol 51 (6) ◽  
pp. 2647-2693 ◽  
Author(s):  
Li-Hui Wang ◽  
Chun-Fu Wu ◽  
Nirmal Rajasekaran ◽  
Young Kee  Shin
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Cellular Localization ◽  
Individual Cell ◽  
Human Cancer ◽  
Predictive Biomarkers ◽  
Suppressor Gene ◽  
Single Mutation ◽  
Multiple Hit

Cancer is a disease caused by the accumulation of genetic and epigenetic changes in two types of genes: tumor suppressor genes (TSGs) and proto-oncogenes. Extensive research has been conducted over the last few decades to elucidate the role of TSGs in cancer development. In cancer, loss of TSG function occurs via the deletion or inactivation of two alleles, according to Knudson’s two-hit model hypothesis. It has become clear that mutations in TSGs are recessive at the level of an individual cell; therefore, a single mutation in a TSG is not sufficient to cause carcinogenesis. However, many studies have identified candidate TSGs that do not conform with this standard definition, including genes inactivated by epigenetic silencing rather than by deletion. In addition, proteasomal degradation by ubiquitination, abnormal cellular localization, and transcriptional regulation are also involved in the inactivation of TSGs. This review incorporates these novel additional mechanisms of TSG inactivation into the existing two-hit model and proposes a revised multiple-hit model that will enable the identification of novel TSGs that can be used as prognostic and predictive biomarkers of cancer.

Role of the p16 tumor suppressor gene in cancer.

1998 ◽  
Vol 16 (3) ◽  
pp. 1197-1206 ◽  
Author(s):  
W H Liggett ◽  
D Sidransky
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Human Cancer ◽  
Suppressor Gene ◽  
Premalignant Lesions ◽  
Early Event ◽  
Cyclin Dependent Kinase ◽  
Primary Tumors

Since its discovery as a CDKI (cyclin-dependent kinase inhibitor) in 1993, the tumor suppressor p16 (INK4A/MTS-1/CDKN2A) has gained widespread importance in cancer. The frequent mutations and deletions of p16 in human cancer cell lines first suggested an important role for p16 in carcinogenesis. This genetic evidence for a causal role was significantly strengthened by the observation that p16 was frequently inactivated in familial melanoma kindreds. Since then, a high frequency of p16 gene alterations were observed in many primary tumors. In human neoplasms, p16 is silenced in at least three ways: homozygous deletion, methylation of the promoter, and point mutation. The first two mechanisms comprise the majority of inactivation events in most primary tumors. Additionally, the loss of p16 may be an early event in cancer progression, because deletion of at least one copy is quite high in some premalignant lesions. p16 is a major target in carcinogenesis, rivaled in frequency only by the p53 tumor-suppressor gene. Its mechanism of action as a CDKI has been elegantly elucidated and involves binding to and inactivating the cyclin D-cyclin-dependent kinase 4 (or 6) complex, and thus renders the retinoblastoma protein inactive. This effect blocks the transcription of important cell-cycle regulatory proteins and results in cell-cycle arrest. Although p16 may be involved in cell senescence, the physiologic role of p16 is still unclear. Future work will focus on studies of the upstream events that lead to p16 expression and its mechanism of regulation, and perhaps lead to better therapeutic strategies that can improve the clinical course of many lethal cancers.

scholarly journals PTEN Gene: A Model for Genetic Diseases in Dermatology

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Corrado Romano ◽  
Carmelo Schepis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Genetic Diseases ◽  
Pten Gene ◽  
The Past ◽  
Front Office ◽  
Near Future

PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN.

scholarly journals The role of PGP9.5 as a tumor suppressor gene in human cancer

2008 ◽  
Vol 123 (4) ◽  
pp. 753-759 ◽  
Author(s):  
Yutaka Tokumaru ◽  
Keishi Yamashita ◽  
Myoung Sook Kim ◽  
Hannah L. Park ◽  
Motonobu Osada ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Human Cancer ◽  
Suppressor Gene

Parenchymal Renal Carcinoma: The Role of the Pathologist

1992 ◽  
Vol 59 (6) ◽  
pp. 16-20
Author(s):  
C. Doglioni
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Prognostic Value ◽  
Renal Carcinoma ◽  
Clinical Course ◽  
Suppressor Gene ◽  
Chromosome 17 ◽  
Growth Fraction ◽  
Prognostic Implications

Renal Cell Carcinoma (RCC) comprises 85% of all primary renal neoplasms. They are frequently diagnosed in an advanced stage and approximately 25% of patients present with metastases at the time of first diagnosis. In RCC pathologists are faced not only with morphologic problems, but also with evaluating parameters that could be utilised in monitoring the clinical course and in prognosis. At present staging, nuclear grading and study of DNA content provide information of prognostic value. However other biological markers are under study: AgNOR, growth fraction, oncogene and tumor-suppressor gene expression and adhesion molecules could provide new valuable information with therapeutic and prognostic implications. There is also a need for the development of sensitive molecular markers for the early detection of RCC: recently nephrocalcin and a guanidinbenzoatase have been proposed as such. The advances in molecular biology and in cytogenetics have shed some light on the pathogenesis of RCC. Alterations in tumor-suppressor genes on chromosome 3 and on chromosome 17 have been frequently observed in most RCC.

scholarly journals Mutant p53 as a Regulator and Target of Autophagy

2021 ◽  
Vol 10 ◽  
Author(s):  
Yong Shi ◽  
Erik Norberg ◽  
Helin Vakifahmetoglu-Norberg
Keyword(s):  
Tumor Suppressor ◽  
High Frequency ◽  
Human Cancer ◽  
Cell Metabolism ◽  
Suppressor Gene ◽  
Mutant P53 ◽  
Wild Type ◽  
Complex Action ◽  
Wild Type P53

One of the most notoriously altered genes in human cancer is the tumor-suppressor TP53, which is mutated with high frequency in more cancers than any other tumor suppressor gene. Beyond the loss of wild-type p53 functions, mutations in the TP53 gene often lead to the expression of full-length proteins with new malignant properties. Among the defined oncogenic functions of mutant p53 is its effect on cell metabolism and autophagy. Due to the importance of autophagy as a stress adaptive response, it is frequently dysfunctional in human cancers. However, the role of p53 is enigmatic in autophagy regulation. While the complex action of the wild-type p53 on autophagy has extensively been described in literature, in this review, we focus on the conceivable role of distinct mutant p53 proteins in regulating different autophagic pathways and further discuss the available evidence suggesting a possible autophagy stimulatory role of mutant p53. Moreover, we describe the involvement of different autophagic pathways in targeting and degrading mutant p53 proteins, exploring the potential strategies of targeting mutant p53 in cancer by autophagy.

scholarly journals Inactivation of X-linked tumor suppressor genes in human cancer

2012 ◽  
Vol 8 (4) ◽  
pp. 463-481 ◽  
Author(s):  
Runhua Liu ◽  
Mandy Kain ◽  
Lizhong Wang
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Human Cancer ◽  
Suppressor Genes

The functional role of tumor suppressor genes in gliomas: Clues for future therapeutic strategies

Neurology ◽  
1998 ◽  
Vol 51 (5) ◽  
pp. 1250-1255 ◽  
Author(s):  
J. Fueyo ◽  
C. Gomez-Manzano ◽  
W. K. Alfred Yung ◽  
A. P. Kyritsis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Functional Role ◽  
Therapeutic Strategies ◽  
Suppressor Genes

scholarly journals KLF2 Inhibits the Migration and Invasion of Prostate Cancer Cells by Downregulating MMP2

2018 ◽  
Vol 13 (1) ◽  
pp. 155798831881690 ◽  
Author(s):  
Binshuai Wang ◽  
Mingyuan Liu ◽  
Yimeng Song ◽  
Changying Li ◽  
Shudong Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cell Function ◽  
Malignant Tumors ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Tumor Tissues ◽  
Luciferase Activity Assay

KLF2, a member of the Kruppel-like factor (KLF) family, is thought to be a tumor suppressor in many kinds of malignant tumors. Its functions in prostate cancer (PCa) are unknown. This study aimed to explore the role of KLF2 in the migration and invasion of PCa cells. The expression of KLF2 was measured by immunohistochemistry in PCa tissues and in paired non-tumor tissues. KLF2 and MMP2 expression in cells was measured by Western blot and RT-qPCR. Adenoviruses and siRNAs were used in cell function tests to investigate the role of KLF2 in regulating MMP2. Interactions between KLF2 and MMP2 were analyzed by a luciferase activity assay. The present study, for the first time, identified that KLF2 was downregulated both in PCa clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2.This study demonstrates that KLF2 might act as a tumor suppressor gene in PCa and that the pharmaceutical upregulation of KLF2 may be a potential approach for treatment.

Sign in / Sign up

Export Citation Format

Share Document