Cervical cancer cells induce apoptosis in TCD4+ lymphocytes through the secretion of TGF-β

López-Muñoz, Hugo; Escobar-Sánchez, Ma. Luisa; López‐Marure, Rebeca; Lascurain-Ledesma, Ricardo; Zenteno, Edgar; Hernández-Vázquez, José M.V.; Weiss‐Steider, Benny; Sánchez-Sánchez, Luis

doi:10.1007/s00404-012-2621-y

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…HPV 16 E7 protein is shown to block the ability of TGF-β to inhibit cell proliferation [ 47 ] suggesting an association of HPV-associated malignant transformation to the loss of responsiveness to the TGF-β-mediated growth inhibitory signal. Cervical cancer cells secrete high levels of TGF-β that inhibit tumor infiltration by apoptosing CD4 lymphocytes evading host immune system [ 17 ]. Moreover, high expression of TGF-β1 predicts poor prognosis in patients with stage Ib-II1 squamous cell carcinoma [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…There is a marked increase in the expression of TGF-β mRNA and protein in human cancers and high expression of TGF-β correlates with more advanced stages of malignancy and decreased survival [ 16 ]. Cervical cancer cells are known to secrete TGF-β [ 17 ], which is capable of augmenting intratumoral stroma and decreasing tumor infiltrate, enhancing tumor growth and metastasis while evading host’s immune system [ 18 ]. The pivotal role of TGF-β in promoting tumor progression suggests that the signaling pathway may be a good target for therapy of cancer [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

Thacker

Karunagaran

2015

PLoS ONE

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Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

Thacker

Karunagaran

2015

PLoS ONE

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“…To the best of our knowledge, the TGF-β/SMAD signaling pathway plays a role in numerous types of cancers, including cervical cancer (15)(16)(17). The TGF-β/SMAD signaling pathway mediated by TGF-β1 is thought to be a key signaling pathway in the regulation of cell proliferation and induction of apoptosis (18).…”

Section: Introductionmentioning

confidence: 99%

“…The TGF-β/SMAD signaling pathway mediated by TGF-β1 is thought to be a key signaling pathway in the regulation of cell proliferation and induction of apoptosis (18). Previous research has revealed that the proliferation and invasion of cervical cancer may be inhibited by TGF-β1 (17). TGF-β binds to TGFBR1 resulting in phosphorylation of the carboxy-terminal serine residue of the SMAD intracellular messenger proteins, SMAD2 and SMAD3 (19).…”

Section: Introductionmentioning

confidence: 99%

Let-7a suppresses cell proliferation via the TGF-β/SMAD signaling pathway in cervical cancer

Chen

Peng

et al. 2016

Oncology Reports

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Cervical cancer is the second most commonly diagnosed type of cancer among women after breast cancer. Recent research has addressed the role of microRNAs in cervical cancer. In the present study, we aimed to determine the effect of let‑7a on the regulation of the cell proliferation of cervical cancer and the related signaling pathway. Real‑time RT‑PCR was used to detect the expression of let‑7a in the blood of cervical cancer patients and normal controls. The expression of let‑7a was also assessed in cervical cancer cell lines: HeLa, SiHa and normal human immortalized keratinocyes HaCaT. Cell proliferation was tested by MTT assay, and cell apoptosis and cell cycle were examined by flow cytometric analysis in HeLa cells. Moreover, bioinformatic analysis, dual‑luciferase reporter assay and western blotting were used to confirm the target gene for let‑7a. In addition, the expression of TGF‑β1, SMAD4 and p53 were assessed by western blotting and real‑time PCR. Our studies showed that the expression of let‑7a in cervical cancer was significantly reduced in cervical cancer patients compared with the expression in the normal control group. Cell proliferation of HeLa cells was inhibited by overexpression of let‑7a. The cell cycle analysis showed that an increased population was arrested in the G2 phase in the let‑7a mimic group when compared with that in the mimic control and untreated groups. In addition, the cell cycle‑related factor p53 was increased in the let‑7a overexpression group compared with that in the control and untreated groups. Furthermore, TGFBR1 was confirmed to be a target of let‑7a. Moreover, the expression of TGF‑β1 and SMAD4 proteins was elevated in cervical squamous carcinoma and cervical adenocarcinoma tissues. However, the expression of TGF‑β1 and SMAD4 was decreased in the let‑7a‑overexpressing cervical cancer cell lines (HeLa, SiHa and CaSki). Our data suggest that let‑7a may play a role in the cell proliferation of cervical cancer by regulating the TGF‑β/SMAD pathway, and may participate in the regulation of the occurrence and development of cervical cancer.

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“…Much of the effect of TGFβ occurs during T cell development in the thymus and lymph nodes 80 , but TGFβ can also have suppressive effects in the context of a tumor milleu 94 . For example, conditioned medium from cervical cancer cell lines decreases lymphocyte proliferation and causes apoptosis in CD4+ cells in a TGFβ- dependent manner in vitro 404 .…”

Section: Immune Interactionsmentioning

confidence: 99%

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

Woodby

Scott

Bodily

2016

Progress in Molecular Biology and Translational Science

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Human papillomaviruses (HPV) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection.

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Cervical cancer cells induce apoptosis in TCD4+ lymphocytes through the secretion of TGF-β

Abstract: Cervical cancer cells secrete TGF-β that inhibits lymphocyte proliferation and induces apoptosis in CD4+, but not in CD8+ lymphocytes.

Cited by 14 publications

References 21 publications

Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

Let-7a suppresses cell proliferation via the TGF-β/SMAD signaling pathway in cervical cancer

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

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