HTLV-1 Tax Stimulates Molecular Events in Various Cancers

Author(s): Wanyi Zhu, Igor F Tsigelny, Valentina L Kouznetsova

The human T-lymphotropic viruses (HTLV) are a family of retroviruses that causes adult T-cell leukemia/lymphoma (ATL). The objective of this study is to elucidate the host genes affected by the HTLV-1 Tax protein, find how host genes are affected, and how this influence is related to several cancer pathways. The DAVID program was used to examine genes affected by Tax, and the gene list was significantly enriched: pancreatic cancer, chronic and acute myeloid leukemia, small cell lung cancer, prostate cancer, non-small cell lung cancer, colorectal cancer, glioma, melanoma, and bladder cancer. The influence of Tax on genes involved in these pathways was studied and the effects on the progression of the pathway were deduced. HTLV-1’s Tax protein contributes epigenetically to the development of different cancers by altering normal transcription and translation, cell cycle signaling systems, and tumor suppressing mechanisms. The discovered effects of Tax on the NF-κB, MAPK, Cyclin-CDK, ErbB, Jak-STAT, VEGF, TGF-β, PI3K-Akt, and β-catenin pathways active during the progression of pancreatic cancer, chronic myeloid leukemia, small cell lung cancer, and colorectal cancer indicates that HTLV-1’s effects are not limited to ATL, can activate cancer-specific biomarkers including ZEB-1, ZEB-2, EZH2, E2F, TRIM33, GLUT1, HK2, PKM2, and LDHA, and can mimic the cancer-specific oncogenes BCR-ABL, K-Ras, and APC. Four signaling networks were elucidated to represent these signaling events, creating a useful representation of an HTLV-1 infection’s role in different cancers, which can aid in identifying and characterizing HTLV-1-associated cancers, determining prognosis, and selecting effective treatments for patients.

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