AF1q Mediates Tumor Progression in Colorectal Cancer by Regulating AKT Signaling

Abstract

The up-regulation of ALL1-fused gene from chromosome 1q (AF1q) is commonly seen in aggressive hematologic malignancies as well as in several solid tumor tissues. However, its expression and intrinsic function in human colorectal cancer (CRC) remains largely undefined. To explore the role of AF1q in human CRC progression, AF1q expression was analyzed in human CRC tissue samples and CRC cell lines. Clinical specimens revealed that AF1q was up-regulated in human CRC tissues, and that this up-regulation was associated with tumor metastasis and late tumor, lymph node, metastasis (TNM) stage. AF1q knockdown by shRNA inhibited tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro, as well as tumorigenesis and liver metastasis in vivo, whereas these effects were reversed following AF1q overexpression. These AF1q-mediated effects were modulated by the protein kinase B (AKT) signaling pathway, and inhibition of AKT signaling attenuated AF1q-induced tumor promotion. Thus, AF1q contributes to CRC tumorigenesis and progression through the activation of the AKT signaling pathway. AF1q might therefore serve as a promising new target in the treatment of CRC.

The Oncogene AF1Q is Associated with WNT and STAT Signaling and Offers a Novel Independent Prognostic Marker in Patients with Resectable Esophageal Cancer

“…AF1q expression is reportedly associated with metastatic spread in colorectal, lung, and breast cancer [5,12,36,37]. Since HER-2 is commonly expressed in EC, lung, and breast cancer [38,39,40,41], HER-2 might be another signaling pathway AF1q interacts with.…”

“…AF1Q was originally identified as an MLL fusion partner in acute myeloid leukemia patients with a t(1; 11)(q21; q23) translocation ( MLLT11 ); here, multiple chromosomal translocations of the AF1q locus have been described [1]. Enhanced AF1q expression is associated with poor clinical outcome in hematologic and several solid malignancies, such as breast, thyroid as well as testicular cancer and neuroblastoma [2,3,4,5,6,7,8,9]. Further on, AF1q plays a role in cell differentiation and maintenance during neuronal development [10], and is involved in stem cell differentiation.…”

“…These two core cancer pathways play a pivotal role in tumors of the gastrointestinal tract and are involved in tumor initiation, progression, metastases, and chemoresistance [13,14]. In colorectal cancer, WNT signaling is a major driver of oncogenicity, and AF1q has been reported to drive proliferation, migration, and invasion in vitro and in vivo [5,15]. Recently, the suppression of breast cancer dissemination has been subscribed to GATA3-driven miR29b induction, which reportedly inhibits AF1q [16].…”

Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers

“…Interesting candidates include MLLT11 and TRIM13, whose CNAs or differential methylation status have not been reported in OSCC . MLLT11 (1q21.3) is an oncogene dysregulated in some acute myeloid leukemia patients with t(1;11)(q21;q23) translocation and also facilitates the progression of solid tumors [ 69 , 70 ]. Recurrent gains of the 1q21.3 region and upregulation of MLLT11 were reported in the Wilms tumor [ 71 ].…”

MLLT11-TRIL complex promotes the progression of endometrial cancer through PI3K/AKT/mTOR signaling pathway

“… 14 , 48 Jingwei Hu et al showed that MLLT11 could regulate the progression of colorectal cancer through AKT. 15 On the other hand, as a component of the TLR4 signaling complex, TRIL plays a vital role in the inflammatory response. 17 , 49 To date, data on the roles of TRIL in tumor development and the specific molecular mechanisms of MLLT11 in regulating AKT remain scant.…”