Evidence that the viral oncoproteins E6 and E7 of HPV induce the expression of a functional IL-2R on cervical cancer cells

Trujillo-Cirilo, Leonardo; Torres-Corioriles, Edgar Ivan; Rangel-Corona, Rosalva; Corona-Ortega, María Teresa; Weiss‐Steider, Benny

doi:10.1016/j.cyto.2021.155592

Cited by 7 publications

(3 citation statements)

References 39 publications

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“…Surprisingly, the more abundant subunit in SiHa cells is IL-2Rγ (85.52%); on the contrary, the beta subunit is barely present (1.5%), and the alpha subunit is not detectable. One report shows the presence of mRNA for the three subunits of IL-2R in the cervical cancer cell line SiHa [22], and the major subunit is IL-2Rγ. However, they do not show the presence of the protein.…”

Section: Discussionmentioning

confidence: 99%

STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa

Valle-Mendiola,

Rocha-Zavaleta,

Maldonado-Lagunas

et al. 2024

IJMS

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The tumor cells reprogram their metabolism to cover their high bioenergetic demands for maintaining uncontrolled growth. This response can be mediated by cytokines such as IL-2, which binds to its receptor and activates the JAK/STAT pathway. Some reports show a correlation between the JAK/STAT pathway and cellular metabolism, since the constitutive activation of STAT proteins promotes glycolysis through the transcriptional activation of genes related to energetic metabolism. However, the role of STAT proteins in the metabolic switch induced by cytokines in cervical cancer remains poorly understood. In this study, we analyzed the effect of IL-2 on the metabolic switch and the role of STAT5 in this response. Our results show that IL-2 induces cervical cancer cell proliferation and the tyrosine phosphorylation of STAT5. Also, it induces an increase in lactate secretion and the ratio of NAD+/NADH, which suggest a metabolic reprogramming of their metabolism. When STAT5 was silenced, the lactate secretion and the NAD+/NADH ratio decreased. Also, the expression of HIF1α and GLUT1 decreased. These results indicate that STAT5 regulates IL-2-induced cell proliferation and the metabolic shift to aerobic glycolysis by regulating genes related to energy metabolism. Our results suggest that STAT proteins modulate the metabolic switch in cervical cancer cells to attend to their high demand of energy required for cell growth and proliferation.

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Section: Discussionmentioning

confidence: 99%

STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa

Valle-Mendiola,

Rocha-Zavaleta,

Maldonado-Lagunas

et al. 2024

IJMS

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“…The studies mentioned above, decreased IL-2 levels in the vaginal microenvironment may affect the clearance of high-risk HPV and lead to persistent infection of high-risk HPV, while persistent infection of high-risk HPV may cause the decreased secretion of IL-2 by local production of E6, E7, etc. ( Trujillo-Cirilo et al., 2021 ), which promotes the development of cervical cancer. Such interactions may be one of the underlying mechanisms that promote the development of CIN and cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Interactions between vaginal local cytokine IL-2 and high-risk human papillomavirus infection with cervical intraepithelial neoplasia in a Chinese population-based study

Wang

Yang

Zhao

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundAlthough interleukin-2 (IL-2) has long been associated with cancer development, its roles in the development of cervical cancer remains unclear. Few studies examined the associations between IL-2 and high-risk human papillomavirus (HPV) with risk of cervical intraepithelial neoplasia (CIN).ObjectiveWe aimed to assess the association of IL-2 and high-risk HPV infection with risk of CIN as well as their interactions on the risk of CIN.DesignWe performed a cross-sectional analysis of screening data in 2285 women aged 19-65 years who participated in an ongoing community-based cohort of 40,000 women in Shanxi, China in 2014-2015. Both categorical and spline analyses were used to evaluation the association between IL-2 in the local vaginal fluids and prevalence of CIN. In addition, 1503 controls were followed up until January 31, 2019), the nested case-control study design was adopted to evaluate the association of vaginal lavage IL-2 levels and the risk of CIN progression.ResultsAfter adjusting for potential confounders, IL-2 levels were statistically inversely associated with prevalence of CIN (the 1st versus 4th quartile IL-2 levels: the respective odds ratio [OR] and 95% confidence intervals [CI] was: = 1.75 [1.37, 2.23] for CIN, 1.32 [1.01, 1.73] for CIN I, and 3.53 [2.26, 5.52] for CIN II/III). Increased IL-2 levels were inversely associated with prevalence of CIN (P-overall<0.01, P-nonlinearity<0.01 for CIN; P-overall<0.01, P-nonlinearity = 0.01 for CIN I; P-overall <0.01, P-nonlinearity = 0.62 for CIN II/III). The highest prevalence of CIN was observed in women with high-risk HPV, who also had the lowest IL-2 levels (P-interaction < 0.01). Nested case-control study observed an inverse association between IL-2 levels and risk of CIN progression (OR=3.43, [1.17, 10.03]).ConclusionsIL-2 levels in the local vaginal fluids were inversely associated with the risk of CIN in Chinese women either with or without high-risk HPV infection.

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“…According to the Human Development Index (HDI) data countries having a lower index showed CC is the second position after breast cancer concerning the incidence and mortality rate and the fourth most common cancer type worldwide (16). A cross-sectional study showed high-risk HPV in China is at least 14.3% among other cancers (47). In India, it is the highest second level among women up to the age of 44 (1).…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus infection

Das¹,

Khan²,

Shamshad³

et al. 2022

ijhs

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In the past decade, cervical cancer has increased alarmingly in different parts of the world especially in developing regions. Cervical cancer is caused by persistent infection with high-risk HPV. Interestingly, HPV infection is associated with other cancers also besides cervical carcinoma. Therefore, a proper understanding of epidemiology, pathophysiology,and treatment and prevention strategy is required to combat this commonly occurring cancer. To eliminate cervical cancer from the global map the only strategy is rigorous vaccination in school-going teenage girls. The WHO wants to eliminate HPV by 2030. Its goal is to vaccinate 90% of females by 2025. However, proper awareness and government initiatives are far behind the required drive. Moreover, the low use of cervical cancer screening techniques like Pap smear and visual inspection with acetic acid hindered HPV infection and cervical cancer control in affected countries. In addition, we try to describe the whole pathological cycle of HPV in humans with prominent risk factors that can be a key to control the incidence of HPV-associated cancers. Finally, we showed the significance of the only available strategy to prevent HPV infection- i.e. vaccination.

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Evidence that the viral oncoproteins E6 and E7 of HPV induce the expression of a functional IL-2R on cervical cancer cells

Cited by 7 publications

References 39 publications

STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa

STAT5 Is Necessary for the Metabolic Switch Induced by IL-2 in Cervical Cancer Cell Line SiHa

Interactions between vaginal local cytokine IL-2 and high-risk human papillomavirus infection with cervical intraepithelial neoplasia in a Chinese population-based study

Human papillomavirus infection

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