Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

Abstract

Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-κB, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, Wnt/β-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effeects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

“…Resistance to cytotoxic chemotherapy has remained a major factor contributing to the poor outcomes observed in patients with pancreatic cancer (20). The activation of STAT3 regulates oncogenic signaling in several types of tumor and leads to increased cell survival, proliferation and tumor growth (21). Activated STAT3 has been considered as a potential biomarker of chemotherapeutic resistance, and inhibition of the STAT3 pathway as a promising treatment strategy for pancreatic tumors (8).…”

Radiation Induces Phosphorylation of STAT3 in a Dose- and Time-dependent Manner

“…STAT3, which was phosphorylated in several clinical cancer cells and considered as the therapeutic target of several cancers, such as colitis-associated cancer (Pandurangan et al, 2014), could be activated by numerous cytokines, growth factors and oncogenic proteins (Bromberg et al, 2001). Alterations in Stat3 phosphorylation status followed with change of cancer cell proliferation, cellular apoptosis and chemo-and radio-therapeutic sensitivity in colorectal cancer, small cell lung cancer, skin cancer cell, ovarian cancer cell and non-small cell lung adenocarcinoma cell line (Abdulghani et al, 2008;Liu et al, 2011;Zhao et al, 2012;Hao et al, 2013;Sun et al, 2013;Zhu et al, 2013).…”

Luteolin, a Bioflavonoid Inhibits Colorectal Cancer through Modulation of Multiple Signaling Pathways: A Review

“…CRC is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately ends up with a phenotypically altered cancer cell (Pitot, 1986). Many signaling pathways are deregulated during the progression of colon cancer (Pandurangan, 2013;Pandurangan and Esa, 2013;Pandurangan and Esa, 2014;). Epidemiological and experimental studies suggest that colon cancer is strongly influenced by nutritional factors, including the amount and composition of dietary fat (Willet et al, 1990;Pandurangan et al, 2013c;He et al, 2014).…”