MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis

Stein, Ulrike; Walther, Wolfgang; Arlt, Franziska; Schwabe, Holger; Smith, Janice; Fichtner, Iduna; Birchmeier, Walter; Schlag, Peter M.

doi:10.1038/nm.1889

Cited by 435 publications

(694 citation statements)

References 41 publications

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“…They determine tumor cells interactions with other cells and with the extracellular matrix, and activate migration, angiogenesis and survival [48]. These genes codified for transcription factors, growth factors receptors, protein kinases and importantly microRNAs [49,50]. Tumor cells interactions with the extracellular matrix are mediated by integrins which trigger invasion and spread.…”

Section: Mechanisms Of Invasion and Metastasismentioning

confidence: 99%

Functional Roles of microRNAs in Cancer: microRNomes and oncomiRs Connection

López‐Camarillo¹,

Marchat²,

Aréchaga-Ocampo³

et al. 2013

Oncogenomics and Cancer Proteomics - Novel Approaches in Biomarkers Discovery and Therapeutic Targets in Cancer

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Section: Mechanisms Of Invasion and Metastasismentioning

confidence: 99%

Functional Roles of microRNAs in Cancer: microRNomes and oncomiRs Connection

López‐Camarillo¹,

Marchat²,

Aréchaga-Ocampo³

et al. 2013

Oncogenomics and Cancer Proteomics - Novel Approaches in Biomarkers Discovery and Therapeutic Targets in Cancer

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“…(5) metastasisassociated colon cancer 1 (MACC1) adında yeni bir gen belirlemişlerdir. MACC1 insanda kromozom 7'de (7p21.1) yerleşiktir ve hücre çoğalması, yayılımı, göçü ve koloni oluşumunu teşvik eder (5). MACC1 mRNA'sının yüksek ifadesi, halen kullanılan Uluslararası Kanserle Mücadele Birliği/Amerika Kanser Komitesi (AJCC/TNM) tümör evrelemeden bağımsız, tümör dokularda yayılım ve kolon kanserlerinin tekrarlaması için önemli bir belirleyicidir (5).…”

Section: Introductionunclassified

“…MACC1 insanda kromozom 7'de (7p21.1) yerleşiktir ve hücre çoğalması, yayılımı, göçü ve koloni oluşumunu teşvik eder (5). MACC1 mRNA'sının yüksek ifadesi, halen kullanılan Uluslararası Kanserle Mücadele Birliği/Amerika Kanser Komitesi (AJCC/TNM) tümör evrelemeden bağımsız, tümör dokularda yayılım ve kolon kanserlerinin tekrarlaması için önemli bir belirleyicidir (5). Birincil tümörlerde 5 yıllık sağkalım oranı, yüksek MACC1 ifadeli hastalar için %15 olan sağkalım oranıyla karşılaştırıldığında, düşük MACC1 ifadeli hastalarda %80'dir (5-7).…”

Section: Introductionunclassified

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Investigation of MACC1-AS1 gene mutations in colorectal cancer

Taib¹,

İğci²,

Borazan³

et al. 2014

Gaziantep Med J

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Colorectal cancer is the frequent cause of mortality in Western world. Metastasis associated with colon cancer 1 (MACC1) gene acts as a key regulator of HGF/Met pathway and is expressed highly in colorectal cancer. MACC1 serves as a prognostic indicator for invasion and metastasis of several cancers. Potential links between MACC1 AS1 RNA locus that located in the intron 6 of MACC1 gene and high expression of MACC1 are unknown. Herein, the secondary structure of MACC-AS1 noncoding RNA and the complementarities between MACC1 mRNA and MACC1-AS1 were analyzed by RNAFold and IntaRNA programs. Since MACC1-AS1 has a proper secondary structure to hybridize with MACC1 mRNA, a potential role of MACC1-AS1 in regulation of MACC1 expression could be thought. The study included 104 controls and 96 patients. Genomic DNA was isolated from blood samples and analyzed by PCR-SSCP and sequence analysis. Three fragments and six genotypes (1, 2, 3, 1&2, 1&3, 2&3) were observed in the exon 1 of MACC1-AS1. A and GT (rs200028381) insertions in genotype 1, G>A substitution and A insertion in genotype 2 were detected. However, no association was observed between these SNPs and colorectal cancer (P>0.05). This is the first investigation on MACC1-AS1 gene mutation in colorectal cancer using molecular techniques. Novel SNPs in exon 1 were identified. In order to understand the association between colorectal tumors and MACC1-AS1 RNA expression clearly; further analysis, like Western blotting and immunohistochemistry of MACC1 and RNA analysis for MACC1-AS1, are needed. Keywords: Colorectal cancer; DNA sequence analysis; MACC1-AS1; mutation screening Özet Kolorektal kanser, batı dünyasında sık gözlenen ölüm nedenlerindendir. Metastazla ilişkili kolon kanseri 1 (MACC1) geni, HGF/Met yolağının anahtar düzenleyicisidir. Kolorektal kanserde yüksek oranda ifade olmaktadır. MACC1 geninin altıncı intronunda MACC1-AS1 karşıt anlamlı RNA bölgesi bulunmaktadır. Bu çalışmada, kodlanmayan MACC1-AS1 RNA'sının ikincil yapısı RNAFold, MACC1 mRNA'sı ile arasındaki etkileşim IntaRNA adlı programlarla analiz edilmiş ve MACC1 gen ifadesinin kontrolünde rol almaya uygun yapısı nedeniyle kolorektal kanserde gözlenen MACC1'in yüksek ifadesi ile ilişkili olabileceği varsayılmıştır. Konu ile ilgili açık bir bilgi bulunmamaktadır. Bu çalışma MACC1'in kodlanmayan bölgesindeki (MACC1-AS1) olası genomik değişimler ve kolorektal kanser arasındaki bağlantıyı araştıran ilk çalışmadır. Çalışmaya 104 kontrol ve 96 hasta birey katılmıştır. Kan örneklerinden elde edilen genomik DNA polimeraz zincir reaksiyonu (PCR) yöntemiyle çoğaltılmış ve tek zincir konformasyon polimorfizmi (SSCP) ile analiz edilmiş ve dizin analizine tabi tutulmuştur. Kontrol ve hasta örneklerinde ekzon 1'de, üç farklı banddan (1, 2, 3) oluşan 6 genotip (1, 2, 3, 1&2, 1&3, 2&3) gözlenmiştir. Dizin analizi neticesinde genotip 1'in bir A eklenmesi ve ayrıca GT eklenmesi (rs200028381), genotip 2'nin ise G>A yer değişimi ve A eklenmesi barındırdığı görülmüş; ancak, genotip 3'te bir farklılık bulunamamışt...

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“…The MDC provided expertise in basic science, collaborative opportunities, and an infrastructure that existed nowhere else in Germany. As an example, the clinical departments each and independently produced a keynote paper 15 years after their founding [7][8][9][10]. Detlev Ganten's vision of the Robert-Rössle Clinic and the Franz-Volhard Clinic adjacent to the MDC campus could not survive the expediencies of later times.…”

mentioning

confidence: 99%

A visionary scientist selects clinicians for clinical research

Luft

2016

J Mol Med

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We celebrate Detlev Ganten's 75th birthday late this March (Fig. 1); we hope he is celebrating too. Detlev Ganten is not only founding editor of the Journal of Molecular Medicine and still active in this capacity, he is also the initial director of the Max-Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. The MDC traces its heritage to the KaiserWilhelm Institute für Hirnforschung, officially founded 1931. The collaboration between Nikolai TimofejewRessovsky, Karl Zimmer, and Max Delbrück that resulted in placing genetics on a molecular footing has been told many times. When the institute was reconstituted after German reunification, Detlev Ganten was given the task of resurrecting the MDC to world-class. And so he did; for 13 years, he was at the helm. Since its founding, 25 years have passed and the MDC has performed even beyond Detlev Ganten's expectations. Of course, since his first two publications appeared in Nature [1] and in Science [2], he probably believes that such publications are easy, as they were for him.Detlev Ganten gave the MDC a unique mission, namely pursuing the highest caliber of disease-oriented (clinical) biological research focusing on the basic mechanisms and molecules of relevance in health and disease and emphasizing the most advanced methodologies in cell biology, genetics, and genomics. He was less interested in the topic and wisely supported the idea that the MDC should pursue a broad spectrum of problems comprising the current chronic scourges, namely cardiovascular disease, cancer, and neurodegenerative disorders. Similarly circumspect, the MDC has maintained this broad base until the present day.Another unique decision Detlev Ganten made was to include clinicians in the field of MDC senior scientists. As the institute had a tradition of encompassing clinical departments since the time of Oskar and Cécile Vogt, the decision was made easier. The institute had continued that tradition and before German reunification had worked intensively with a clinic dedicated to cancer and a clinic for cardiovascular diseases in the framework of the BAcademy of the Sciences^. However, although the clinics were still there, the framework was gone and to continue the concept in conjunction with the two medical schools Berlin had in 1991 was difficult. Furthermore, the mission Detlev Ganten espoused was not necessarily commensurate with the usual department chairmanships in academic medicine. Clinical excellence, teaching, and research were the appropriate criteria of the time; however, Detlev Ganten wanted the order and emphasis revised and reversed. Research at an internationally competitive level was to receive priority, yet the clinical departments also had to work; the patient care had to be excellent, and the teaching mission was not to be ignored. He found his clinicians and the search also underscores the value of personal relationships when making personnel decisions.

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MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis

Cited by 435 publications

References 41 publications

Functional Roles of microRNAs in Cancer: microRNomes and oncomiRs Connection

Functional Roles of microRNAs in Cancer: microRNomes and oncomiRs Connection

Investigation of MACC1-AS1 gene mutations in colorectal cancer

A visionary scientist selects clinicians for clinical research

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