POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines

Amunjela, Johanna Ndamwena; Tucker, Steven

doi:10.1016/j.canlet.2017.08.002

Cited by 16 publications

(32 citation statements)

References 30 publications

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“…Given that cAMP inhibits growth in breast cancer cell lines and tissues, while EPAC and PKA promote these effects, it is unlikely that cAMP-mediated inhibition of breast cancer cell migration is mediated via EPAC and PKA. However, cAMP-mediated inhibition of breast cancer cell adhesion, migration and proliferation are consistent with the effects seen after forced expression of POPDC1 in breast cancer cells [37,43]. It is thus likely that the anti-tumorigenic effects of cAMP are mediated via POPDC1.…”

Section: The Roles Of Popdc Proteins In Cell Proliferationsupporting

confidence: 65%

“…To date, evidence on the effects of POPDC1 on cell proliferation and its interaction with molecules in pathways that regulate cell proliferation such as Zonula occludens-1 (ZO-1), Wnt and c-Myc, are consistent with POPDC1 being a regulator of cell proliferation and its loss or suppression of function enhancing malignant cell behavior [7,10,41,42]. The loss of POPDC1 function has further been shown to enhance cell migration, proliferation, and invasion in many solid tumors [10,37,38,[42][43][44]. Furthermore, POPDC1 expression is significantly suppressed at all clinical stages of breast [43] and gastric cancer [45] without correlation to clinical progression.…”

Section: The Roles Of Popdc Proteins In Cell Proliferationmentioning

confidence: 91%

“…In contrast to POPDC1, POPDC2 and POPDC3, have been associated with both oncogenic and tumor suppressor roles in different cancer types suggesting that these proteins might serve tissue-specific functions. In a recent study that examined the expression of POPDC proteins in ductal breast carcinoma, POPDC2 and POPDC3 were found to be significantly overexpressed in breast cancer tissues [43]. Enhanced expression of POPDC2 was observed at all clinical stages of breast cancer while POPDC3 was only expressed at higher levels in early stages of the disease [43].…”

Section: The Roles Of Popdc Proteins In Cell Proliferationmentioning

confidence: 99%

“…The loss of POPDC1 function has further been shown to enhance cell migration, proliferation, and invasion in many solid tumors [10,37,38,[42][43][44]. Furthermore, POPDC1 expression is significantly suppressed at all clinical stages of breast [43] and gastric cancer [45] without correlation to clinical progression. Indeed, the findings from these studies support the hypothesis that POPDC1 is a tumor suppressor of multiple cancer types.…”

Section: The Roles Of Popdc Proteins In Cell Proliferationmentioning

confidence: 99%

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The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Amunjela

Swan

Brand

2019

Cells

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The Popeye domain containing (POPDC) gene family consists of POPDC1 (also known as BVES), POPDC2 and POPDC3 and encodes a novel class of cyclic adenosine monophosphate (cAMP) effector proteins. Despite first reports of their isolation and initial characterization at the protein level dating back 20 years, only recently major advances in defining their biological functions and disease association have been made. Loss-of-function experiments in mice and zebrafish established an important role in skeletal muscle regeneration, heart rhythm control and stress signaling. Patients suffering from muscular dystrophy and atrioventricular block were found to carry missense and nonsense mutations in either of the three POPDC genes, which suggests an important function in the control of striated muscle homeostasis. However, POPDC genes are also expressed in a number of epithelial cells and function as tumor suppressor genes involved in the control of epithelial structure, tight junction formation and signaling. Suppression of POPDC genes enhances tumor cell proliferation, migration, invasion and metastasis in a variety of human cancers, thus promoting a malignant phenotype. Moreover, downregulation of POPDC1 and POPDC3 expression in different cancer types has been associated with poor prognosis. However, high POPDC3 expression has also been correlated to poor clinical prognosis in head and neck squamous cell carcinoma, suggesting that POPDC3 potentially plays different roles in the progression of different types of cancer. Interestingly, a gain of POPDC1 function in tumor cells inhibits cell proliferation, migration and invasion thereby reducing malignancy. Furthermore, POPDC proteins have been implicated in the control of cell cycle genes and epidermal growth factor and Wnt signaling. Work in tumor cell lines suggest that cyclic nucleotide binding may also be important in epithelial cells. Thus, POPDC proteins have a prominent role in tissue homeostasis and cellular signaling in both epithelia and striated muscle.

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Section: The Roles Of Popdc Proteins In Cell Proliferationsupporting

confidence: 65%

Section: The Roles Of Popdc Proteins In Cell Proliferationmentioning

confidence: 91%

Section: The Roles Of Popdc Proteins In Cell Proliferationmentioning

confidence: 99%

Section: The Roles Of Popdc Proteins In Cell Proliferationmentioning

confidence: 99%

See 2 more Smart Citations

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Amunjela

Swan

Brand

2019

Cells

Self Cite

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“…64 While several studies have demonstrated that BVES has an important role in intestinal malignancy, additional studies implicate BVES in hepatocellular and breast cancer. [65][66][67] The tissue-specific functions of BVES in regulating tumorigenesis remain unclear, especially in vivo, but the recent literature strongly suggests BVES acts as a tumor suppressor in a variety of epithelial tissues, likely, at least in part, due to its role in promoting c-Myc degradation. The majority of phenotypes associated with BVES loss require cellular or physiologic stress, suggesting that under homeostasis, BVES loss has minimal deleterious effects.…”

Section: Bves As a Tumor Suppressormentioning

confidence: 99%

Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer

2018

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Blood vessel epicardial substance (BVES) is a tight-junction associated protein that was originally discovered from a cDNA screen of the developing heart. Research over the last decade has shown that not only is BVES is expressed in cardiac and skeletal tissue, but BVES is also is expressed throughout the gastrointestinal epithelium. Mice lacking BVES sustain worse intestinal injury and inflammation. Furthermore, BVES is suppressed in gastrointestinal cancers, and mouse modeling has shown that loss of BVES promotes tumor formation. Recent work from multiple laboratories has revealed that BVES can regulate several molecular pathways, including cAMP, WNT, and promoting the degradation of the oncogene, c-Myc. This review will summarize our current understanding of how BVES regulates the intestinal epithelium and discuss how BVES functions at the molecular level to preserve epithelial phenotypes and suppress tumorigenesis. ARTICLE HISTORY

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The Popeye domain containing gene family encoding a family of cAMP-effector proteins with important functions in striated muscle and beyond

Swan

Gruscheski

Boland

et al. 2019

J Muscle Res Cell Motil

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The Popeye domain containing (POPDC) gene family encodes a novel class of membrane-bound cyclic AMP effector proteins. POPDC proteins are abundantly expressed in cardiac and skeletal muscle. Consistent with its predominant expression in striated muscle, Popdc1 and Popdc2 null mutants in mouse and zebrafish develop cardiac arrhythmia and muscular dystrophy. Likewise, mutations in POPDC genes in patients have been associated with cardiac arrhythmia and muscular dystrophy phenotypes. A membrane trafficking function has been identified in this context. POPDC proteins have also been linked to tumour formation. Here, POPDC1 plays a role as a tumour suppressor by limiting c-Myc and WNT signalling. Currently, a common functional link between POPDC's role in striated muscle and as a tumour suppressor is lacking. We also discuss several alternative working models to better understand POPDC protein function.

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POPDC1 is suppressed in human breast cancer tissues and is negatively regulated by EGFR in breast cancer cell lines

Cited by 16 publications

References 30 publications

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

The Role of the Popeye Domain Containing Gene Family in Organ Homeostasis

Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer

The Popeye domain containing gene family encoding a family of cAMP-effector proteins with important functions in striated muscle and beyond

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