A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts

Kabir, Tasnuva D.; Leigh, Ross J; Tasena, Hataitip; Mellone, Massimiliano; Coletta, Ricardo D.; Parkinson, Eric Kenneth; Prime, Stephen S.; Thomas, Gareth J.; Paterson, Ian C.; Zhou, Dongfang; McCall, John L.; Speight, Paul M.; Lambert, D

doi:10.18632/aging.100987

Cited by 61 publications

(51 citation statements)

References 43 publications

(53 reference statements)

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“…Higher levels of miR-335 lowered the abundance of phosphatase and tensin homologue (PTEN), in turn causing a rise in SASP factors like MMP2 and IL6 [55]. Senescent cells showed increased secretion of the protein cyclooxygenase 2 (PTGS2/COX2) and the signaling lipid prostaglandin E2 (PGE2).…”

Section: Micrornasmentioning

confidence: 99%

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SASP regulation by noncoding RNA

Panda

Abdelmohsen

Gorospe

2017

Mechanisms of Ageing and Development

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Noncoding RNAs (ncRNAs), including micro (mi)RNAs, long noncoding (lnc)RNAs, and circular (circ)RNAs, control specific gene expression programs by regulating transcriptional, post-transcriptional, and post-translational processes. Through their broad influence on protein expression and function, ncRNAs have been implicated in virtually all cellular processes such as proliferation, senescence, quiescence, differentiation, apoptosis, and the stress and immune responses. Senescence is a cellular phenotype associated with the physiologic decline of aging and with age-related pathologies. Besides their characteristic terminal growth arrest and differential gene expression programs, senescent cells are known to secrete potent pro-inflammatory, angiogenic, and tissue-remodeling factors. This important trait, known as the senescence-associated secretory phenotype (SASP), influences many biological processes such as tissue repair and regeneration, tumorigenesis, and the aging-associated pro-inflammatory state. Here, we review the microRNAs, lncRNAs, and circRNAs that influence the production of SASP factors and discuss the rising interest in SASP-regulatory ncRNAs as diagnostic and therapeutic targets.

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Section: Micrornasmentioning

confidence: 99%

“…Senescent cells showed increased secretion of the protein cyclooxygenase 2 (PTGS2/COX2) and the signaling lipid prostaglandin E2 (PGE2). The levels of miR-335 were downregulated by inhibition of PTSG2/COX2 using celecoxib, which restored PTEN expression and decreased SASP [55]. …”

Section: Micrornasmentioning

confidence: 99%

SASP regulation by noncoding RNA

Panda

Abdelmohsen

Gorospe

2017

Mechanisms of Ageing and Development

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“…One of the ways in which this COX-2 upregulation may lead to eventual loss of MTSS1 expression is through inflammation-mediated proteasome upregulation. Interleukin-6 (IL-6) is a known COX-2 dependent cytokine that exerts its effects through activation of oncogenic signaling pathways involved STAT3 [58, 59]. It has been shown that IL-6 upregulation can lead to increase in proteasome expression [60, 61].…”

Section: Discussionmentioning

confidence: 99%

Loss of MTSS1 results in increased metastatic potential in pancreatic cancer

et al. 2017

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Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of 7%. This dismal prognosis is largely due to the inability to diagnose the disease before metastasis occurs. Tumor cell dissemination occurs early in PDAC. While it is known that inflammation facilitates this process, the underlying mechanisms responsible for this progression have not been fully characterized. Here, we functionally test the role of metastasis suppressor 1 (MTSS1) in PDAC. Despite evidence showing that MTSS1 could be important for regulating metastasis in many different cancers, its function in PDAC has not been studied. Here, we show that loss of MTSS1 leads to increased invasion and migration in PDAC cell lines. Moreover, PDAC cells treated with cancer-associated fibroblast-conditioned media also have increased metastatic potential, which is augmented by loss of MTSS1. Finally, overexpression of MTSS1 in PDAC cell lines leads to a loss of migratory potential in vitro and an increase in overall survival in vivo. Collectively, our data provide insight into an important role for MTSS1 in suppressing tumor cell invasion and migration driven by the tumor microenvironment and suggest that therapeutic strategies aimed at increasing MTSS1 levels may effectively slow the development of metastatic lesions, increasing survival of patients with PDAC.

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“…And rapamycin, a clinically approved drug, inhibit cancer by targeting stromal fibroblasts. 40,41 Meanwhile a study found that NAC inhibits mTOR. 42 And the results in our study demonstrated that oxidative stress induced by colorectal cancer cells could stimulate autophagy in CAFs, which then led to intensive glycolysis and attenuated aerobic oxidation.…”

Section: Ccd-18-co Cell Viability (%)mentioning

confidence: 99%

Oxidative stress induced autophagy in cancer associated fibroblast enhances proliferation and metabolism of colorectal cancer cells

Zhou

Wang

et al. 2016

Cell Cycle

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Tumors are comprised of malignant cancer cells and stromal cells which constitute the tumor microenvironment (TME). Previous studies have shown that cancer associated fibroblast (CAF) in TME is an important promoter of tumor initiation and progression. However, the underlying molecular mechanisms by which CAFs influence the growth of colorectal cancer cells (CRCs) have not been clearly elucidated. In this study, by using a non-contact co-culture system between human colorectal fibroblasts (CCD-18-co) and CRCs (LoVo, SW480, and SW620), we found that fibroblasts existing in tumor microenvironment positively influenced the metabolism of colorectal cancer cells, through its autophagy and oxidative stress pathway which were initially induced by neighboring tumor cells. Therefore, our data provided a novel possibility to develop fibroblasts as a potential target to treat CRC.

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A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts

Cited by 61 publications

References 43 publications

SASP regulation by noncoding RNA

SASP regulation by noncoding RNA

Loss of MTSS1 results in increased metastatic potential in pancreatic cancer

Oxidative stress induced autophagy in cancer associated fibroblast enhances proliferation and metabolism of colorectal cancer cells

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