Historical retrospective of the SRC oncogene and new perspectives (Review)

Abstract

Since its first discovery as part of the Rous sarcoma virus (RSV) genome, the c-SRC (SRC) proto-oncogene has been proved a key regulator of cancer development and progression, and thus it has been highlighted as an attractive target for anti-cancer therapeutic strategies. Though the exact mechanisms of its action are still not fully understood, SRC protein mediates crucial normal cell functions, such as cell development, proliferation and survival, and its dysregulation is considered as an oncogenic signature and a driving force for cancer initiation. In the present review, we present a flashback to the history of the Src research, while focusing on the most important milestones in the field. Moreover, we investigate the proposed regulatory mechanisms and molecules that mediate its action in order to designate putative therapeutic targets and useful prognostic and/or diagnostic tools. Furthermore, we present and discuss existing therapeutic approaches that are explored in clinical settings. Contents 1. Introduction 2. Discovery of Rous sarcoma virus 3. Cellular origin of retroviral oncogenes 4. MicroRNAs as the fine tuners of SRC oncogenic signaling 5. miRNA-mediated SRC oncogenic signaling in selected cancer types 6. Exosomes as the fine tuners of oncogenic signaling 7. SRC inhibitors as anticancer agents in clinical trials 8. Conclusion

TRIM7 suppresses cell invasion and migration through inhibiting HIF‐1α accumulation in clear cell renal cell carcinoma

“…A recent study reported that TRIM7 targets the proto-oncogene Src for lys48-linked polyubiquitination and degradation (Zhu et al, 2020). Moreover, Src plays an important role in the regulation of HIF-1α levels (Chou et al, 2010; Lee et al, 2011;Simatou et al, 2020). Thus, we investigated whether TRIM7 regulates HIF-1α signaling by targeting Src.…”

“…The proto-oncogene Src is a non-receptor tyrosine kinase that regulates a wide range of cellular events, including cell growth, differentiation, proliferation, survival, adhesion, migration, and motility (Simatou et al, 2020). In normal cells, Src is strictly regulated at both the transcriptional and post-translational levels by a variety of mechanisms.…”

“…As a nonreceptor protein tyrosine kinase, Src, once activated, triggers multiple downstream signaling pathways, including the PI3K/AKT/ mTOR signaling pathway (Simatou et al, 2020). Moreover, it has been demonstrated that HIF1A mRNA translation is dependent on mTOR in certain cellular contexts (Dodd et al, 2015;Thomas et al, 2006).…”

Correlation of SARS‑CoV‑2 to cancer: Carcinogenic or anticancer? (Review)

“…Instead, tumor viruses can control the complex genome of host cells, promoting unrestricted cell proliferation (13)(14)(15). Experiments on induction of chicken sarcoma by Rous virus demonstrate that virus infection can successfully induce tumor formation (16,17), showing that tumors can either develop spontaneously in organisms or be formed by virus induction. The above observation has laid a foundation for the following in vitro tumor cell cultures and in vivo transfection in mice.…”

“…The above observation has laid a foundation for the following in vitro tumor cell cultures and in vivo transfection in mice. It has been shown that infection of Rous virus leads to the occurrence of tumor cell traits in the cultured cells in vitro, which include a loss of contact inhibition, continued proliferation and anchoring independence (17). To date, several tumor viruses have been identified, including human herpes virus 8 (HHV-8) (18)(19)(20), human papilloma virus (HPV) (19,(21)(22)(23)(24)(25)(26)(27), hepatitis B virus (HBV) (19,(28)(29)(30), Epstein-Barr virus (EBV) (19,26,(31)(32)(33)(34)(35), Cytomegalovirus (CMV) (19,27,(36)(37)(38), human immunodeficiency virus (HIV) (19,(39)(40)(41)(42), human T cell lymphotropic virus (HTLV) (43,44) and hepatitis C virus (HCV) (45)(46)(47)(48) (Fig.…”