MACC1

Official Full Name

MET transcriptional regulator MACC1

Organism

Homo sapiens

GeneID

346389

Background

MACC1 is a key regulator of the hepatocyte growth factor (HGF; MIM 142409)-HGF receptor (HGFR, or MET; MIM 164860) pathway, which is involved in cellular growth, epithelial-mesenchymal transition, angiogenesis, cell motility, invasiveness, and metastasis. Expression of MACC1 in colon cancer (MIM 114500) specimens is an independent prognostic indicator for metastasis formation and metastasis-free survival (Stein et al., 2009 [PubMed 19098908]).[supplied by OMIM, Mar 2009]

Synonyms

7A5; SH3BP4L;

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Detailed Information

Brief Introduction

MACC1 is a gene closely related to colon cancer, which is found in the primary and metastatic lesions by whole-gene expression analysis. MACC1 can predict metastasis and tumor free survival of colon cancer. Furthermore, MACC1 can be used as a prognostic marker for metastasis of colon cancer, independent of clinical variables such as age, sex, tumor invasion, lymph node status, and lymphatic invasion. The MACC1 gene is located on human chromosome 7 (7p21.1). It is noteworthy that the hepatocyte growth factor (HGF) and its receptor c-Met (c-met proto-oncogene) are also located on chromosome 7 (7q21.1 and 7q31.2), which are the major signal transduction pathways involved in MACC1.

MACC1 Structure

The cDNA encoded by MACC1 contains 2,559 nucleotides, which encode 825 amino acids including ZU5 domain, SH3 domain, proline-rich motif, DD1 domain and DD2 domain. About 130-150 amino acids in the N-terminal region of the MACC1 gene contain conserved sequence sites for protein interactions. The ZU5 domain to the C-end contains a SH3 binding motif, followed by the variant SH3 domain. These domains and binding motifs are located in the same molecule and can mediate protein-protein interactions via a tyrosine kinase-dependent signal transduction pathway, which is essential for the biological functions of MACC1. When the SH3 domain or proline-rich sequence is deleted, MACC1 transfers from the cytoplasm to the nucleus, and the ability to activate c-Met transcription disappears. At C-terminal, MACC1 has two distinct death domains, DD1 and DD2. Its typical function is to regulate the formation of oligomeric signal complexes and mediate the binding of other DDS proteins in the induction of apoptotic signals. The central and C-terminal regions of MACC1 contain tyrosine phosphorylation sites that bind to proteins comprising the SH2 domains, such as tyrosine protein kinases, phosphatases, and junctional proteins.

MACC1 and HGF/c-Met Signal Transduction Pathway

HGF/c-Met signal transduction pathway plays an important role in embryonic development and tissue repair under physiological conditions. Abnormal HGF/c-Met signal transduction pathway is closely related to the occurrence of malignant tumors, especially the invasion and metastasis of malignant tumors. When HGF binds to the c-Met promoter and activates the HGF/c-Met signal transduction pathway, an increase in the number of c-Met proteins binds to more HGF. HGF then induces MACC1 to enter the nucleus from cytoplasm, driving the positive feedback loop of MACC1, leading to cell growth, epithelial mesenchymal transition, angiogenesis, cell movement, invasion and metastasis.

MACC1 Gene and Malignant Tumors

MACC1 has the highest expression in colon cancer, followed by other gastrointestinal cancers. The expression of MACC1 in colonic mucosa, adenoma, primary and metastatic tissues increases in turn, which suggests that the increased expression of MACC1 is associated with the transformation of benign tissues into malignant lesions and reflects the metastatic ability of primary tumors. The high expression of c-Met mRNA and protein in colorectal cancer, ileum and small intestinal cancer, gastric cancer, liver cancer, pancreatic cancer and ovarian cancer (compared with normal tissues) suggests that MACC1 may be involved in various malignant tumors other than colon cancer.

References:

Liao Xiaochun, et al. Advances in metastasis-related gene-1 in colon cancer [J]. Practical preventive medicine, 2017, (4).
Zhou Na, et al. MACC1 gene and cancer [J]. Chinese Journal of cancer prevention, 2013, (3).
Xu Chunyan, et al. MACC1 in the occurrence and development of tumor and its expression regulation mechanism [J]. Gastroenterology, 2014, (11).

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