IGF axis and other factors in HPV-related and HPV-unrelated carcinogenesis (Review)

Abstract

The insulin-like growth factor (IGF) axis promotes the growth of cells, tissues and organs. IGF-1 is mainly produced in the liver but is also secreted from local tissues. In the circulation, IGF-1 is bound to insulin-like binding proteins (IGFBPs), and when released it activates the insulin-like growth factor receptor (IGF-1R). The signal is further transmitted by intracellular signaling pathways leading to gene expression that regulates, among others, cell proliferation and survival. This review presents the IGF axis in the context of cell transformation and cancer development. Aspects involving IGF-1 deficiency and protection from cancer are also briefly described. Furthermore, human papillomaviruses (HPVs) interplaying with IGF axis components in cervical cancer development are described. These small dsDNA viruses are divided into low-risk and high-risk HPVs with regard to the potency of their oncogenic actions; they mainly infect epithelial or mucosal cells. Special attention is drawn to expression of two major HPV oncogenes (E6 and E7) initiating and maintaining cervical carcinogenesis, which is a multistep and multifactorial process; therefore, involvement of additional factors such as mitochondrial DNA changes, sex hormones, retinoic and folic acids are also discussed. Finally, IGF axis components and HPV oncogenes as targets in anticancer treatment are presented which include IGF-1R downregulation, RNA interference and anti-HPV therapeutic vaccines. The review concludes that despite an enormous advancement in research on IGF and HPV-related cancers, more molecular studies and clinical trials are needed before commercialized therapies are widely available for oncology patients.

Correlation of E6 and E7 levels in high-risk HPV16 type cervical lesions with CCL20 and Langerhans cells

“…On the other hand, it has also been found that HPV infection can escape immune surveillance and response. Thus, research on the mechanisms underlying the latter phenomenon has important significance (Durzynska, 2014).…”

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

“…It was reported that the IGF1 axis is important for proliferation of certain tumor types (reviewed e.g. by Pollak (2008) and Durzyń ska et al (2014)), but it is not known whether insulin effects on tumor progression are mediated via the insulin or the IGF1 receptor. In order to distinguish between insulin actions via IR vs IGF1R we aimed to reduce expression of the IR by lentiviral shRNA KD.…”

A patient with solid gynecologic cancer causing lactic acidosis, severe hypercalcemia, and hypoglycemia

“…IGFs are multifunctional peptides that play a pivotal role in cell regulation; they consist of IGF‐1 and IGF‐2, with three cell‐membrane receptors and IGF‐binding proteins. These factors can play an important paracrine/autocrine role in promoting tumor growth during tumor progression; however, these roles vary depending on the tissue origin . IGF‐1 may also be a useful biomarker for assessing risk and early diagnosis of precancerous growth in the cervix, and IGF‐2 may be a reliable marker for early diagnosis and the monitoring of therapy efficacy …”

“…These factors can play an important paracrine/autocrine role in promoting tumor growth during tumor progression; however, these roles vary depending on the tissue origin. [19][20][21] IGF-1 may also be a useful biomarker for assessing risk and early diagnosis of precancerous growth in the cervix, 22 and IGF-2 may be a reliable marker for early diagnosis and the monitoring of therapy efficacy. 23…”