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MACC1-the first decade of a key metastasis molecule from gene discovery to clinical translation
Harikrishnan Radhakrishnan1, Wolfgang Walther1,2, Fabian Zincke1,2
1Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Abstract:
Deciphering the paths to metastasis and identifying key molecules driving this process is one important issue for understanding and treatment of cancer. Such a key driver molecule is Metastasis Associated in Colon Cancer 1 (MACC1). A decade long research on this evolutionarily conserved molecule with features of a transcription factor as well as an adapter protein for versatile protein-protein interactions has shown that it has manifold properties driving tumors to their metastatic stage. MACC1 transcriptionally regulates genes involved in epithelial-mesenchymal transition (EMT), including those which are able to directly induce metastasis like c-MET, impacts tumor cell migration and invasion, and induces metastasis in solid cancers. MACC1 has proven as a valuable biomarker for prognosis of metastasis formation linked to patient survival and gives promise to also act as a predictive marker for individualized therapies in a broad variety of cancers. This review discusses the many features of MACC1 in the context of the hallmarks of cancer and the potential of this molecule as biomarker and novel therapeutic target for restriction and prevention of metastasis.
Insights
Metastasis Associated in Colon Cancer 1 (MACC1) drives tumor metastasis by regulating epithelial-mesenchymal transition and impacting cell migration. MACC1 shows promise as a biomarker for cancer prognosis and a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastasis is a critical challenge in cancer treatment.
- Identifying key drivers of metastasis is crucial for developing effective therapies.
- Metastasis Associated in Colon Cancer 1 (MACC1) is an evolutionarily conserved molecule implicated in cancer progression.
Purpose of the Study:
- To review the multifaceted roles of MACC1 in cancer metastasis.
- To explore MACC1's potential as a prognostic and predictive biomarker.
- To discuss MACC1 as a therapeutic target for preventing and restricting metastasis.
Main Methods:
- Literature review of studies on MACC1 function and clinical relevance.
- Analysis of MACC1's role in regulating epithelial-mesenchymal transition (EMT).
- Evaluation of MACC1's impact on tumor cell migration, invasion, and metastasis.
Main Results:
- MACC1 acts as a transcription factor and adapter protein, driving tumors to a metastatic stage.
- MACC1 regulates genes involved in EMT, including c-MET, promoting metastasis.
- MACC1 influences tumor cell migration and invasion, inducing metastasis in solid cancers.
Conclusions:
- MACC1 is a significant driver of cancer metastasis with diverse molecular functions.
- MACC1 serves as a valuable prognostic biomarker for metastasis and patient survival.
- MACC1 presents a promising target for novel anti-metastasis therapies and personalized cancer treatment.
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