HOXB8 enhances the proliferation and metastasis of colorectal cancer cells by promoting EMT via STAT3 activation

Abstract

BackgroundPrevious studies have demonstrated that the expression of homeobox8 (HOXB8) is higher in colorectal cancer (CRC) tissues than in normal tissues; however, the precise role of HOXB8 in human CRC cells remains to be elucidated.MethodsWe generated lentiviral constructs to overexpress and silence HOXB8 in CRC cell lines, and examined their biological functions through MTT, wound healing, colony and transwell, expression of signal transducer and activator of transcription 3 (STAT3) and epithelial–mesenchymal transition (EMT) related factors through western-blot.ResultsHOXB8 knockdown inhibited cellular proliferation and invasion in vitro as well as carcinogenesis and metastasis in vivo. HOXB8 also induced EMT, which is characterized by the down-regulation of E-cadherin and the up-regulation of Vimentin, N-cadherin, Twist, Zeb1 and Zeb2. Moreover, HOXB8 activated STAT3, which is known to play an oncogenic role in diverse human malignancies.ConclusionsOur results indicate that HOXB8 may be an independent prognostic factor in CRC. Therefore, deserved a deeper research.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0717-6) contains supplementary material, which is available to authorized users.

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Moreover, STAT3 was upregulated in TGF‐β1‐induced EMT during renal fibrosis, implying that STAT3 is an innovative target for the prevention of fibrosis . Furthermore, there are many mediators that induce EMT through the activation of STAT3, such as Pin1, HOXB8, miR‐30d, and IL‐6 …”

“…111 Furthermore, there are many mediators that induce EMT through the activation of STAT3, such as Pin1, HOXB8, miR-30d, and IL-6. [112][113][114][115] Sepantronium bromide is an inhibitor of survivin that exhibits anticancer properties in multiple cancer types. A recent study revealed that sepantronium bromide reduced the invasion of glioblastoma induced by radiation and reversed EMT by targeting STAT3.…”

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

“…JAK/STAT3 signaling also can be induced by oncoproteins, including RPL34 [125], HOXB8 [126], CD146 [127], and Akirin2 [128]. This recently recognized regulation of new oncogenes involved in activating JAK/STAT3/VEGFA, NF-κB, and ERK signaling might provide crucial targets to block the cancer progression.…”

Mortalin contributes to colorectal cancer by promoting proliferation and epithelial–mesenchymal transition

“…Colorectal cancer (CRC), a common lethal tumor of the digestive tract, is the third commonly diagnosed cancer (10.2%) and the second leading cause of cancer‐related deaths in the world . Metastasis is one of the major reasons CRC patients to resume treatment . It is important to understand the mechanism of carcinogenesis and development, as CRC threaten human health and lives.…”

“…1 Metastasis is one of the major reasons CRC patients to resume treatment. 2,3 It is important to understand the mechanism of carcinogenesis and development, as CRC threaten human health and lives. Thus, elucidating the underlying mechanisms of the cause and progression of CRC is a clinical priority.…”