Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions

Linxweiler, Maximilian; Bochen, Florian; Schick, Bernhard; Wemmert, Silke; Kadah, Basel Al; Greiner, Markus; Hasenfus, Andrea; Bohle, Rainer-Maria; Juhasz-Böss, Ingolf; Solomayer, Erich‐Franz; Takács, Zoltán

doi:10.1186/s12885-016-2739-6

Cited by 28 publications

(51 citation statements)

References 49 publications

(74 reference statements)

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“…To identify further roles of Sec62 in tumor cell biology apart from the known function in protein translocation across the ER membrane, several studies investigated the effect of SEC62 silencing and SEC62 overexpression on neoplastic and non-neoplastic human cell lines. Consistently, a SEC62 knockdown markedly reduced the migration and invasion potential of prostate cancer cells 90 as well as the migration of NSCLC cells, 90 thyroid cancer cells 90 and cervical cancer cells, 91 whereas SEC62 overexpression stimulated the migration of cervical cancer cells 91 and even human embryonic kidney cells. 90 The latter is particularly telling since it provided a direct link between Sec62 and cell migration.…”

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 57%

“…Of note, neither SEC62 silencing nor SEC62 overexpression markedly affected cell proliferation in these studies. 89–91 However, other studies reported an impairment of cell proliferation in Sec62-depleted cell lines harboring a 3q26 amplification 102 as well as in Sec62-depleted HeLa cells. 32 Though all of these studies indicate a crucial role of SEC62 in cancer cell migration and invasion—molecular processes that are essential for tumor metastasis—it is not yet clear how this function of Sec62 is mediated on the molecular level.…”

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 89%

“…On the whole, all studies addressing the expression of SEC62 in human cancer so far consistently reported an increased SEC62 expression level for the majority of investigated cases both in the tumor tissue 88–92 , 94 and in peripheral blood mononuclear cells, 93 suggesting that SEC62 plays a crucial role in the pathogenesis of various tumor entities and bears a potential oncogenic function. This hypothesis is further substantiated by the fact that the SEC62 -encoding chromosomal region 3q26 is amplified in numerous human cancer entities including cervical cancer, 95 , 96 non-small-cell lung cancer, 97 esophageal cancer, 98 ovarian cancer, 99 and head and neck cancer.…”

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 93%

“…For thyroid cancer, increased Sec62 protein levels were observed in 40% and increased SEC62 -mRNA levels in 60% of cases. A study focusing on SEC62 expression in dysplastic cervical lesions 91 found SEC62 amplifications in 23% and increased Sec62 protein levels in 100% of cervical cancer cases with a gradually increasing SEC62 expression depending on the severity of dysplasia. Wemmert et al 92 investigated the expression of SEC62 in 35 cases of head and neck squamous cell carcinomas using immunohistochemistry and found a strong staining intensity in 34% and a moderate staining intensity in 23% of cases.…”

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 99%

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Let’s talk about Secs: Sec61, Sec62 and Sec63 in signal transduction, oncology and personalized medicine

Linxweiler

Schick

Zimmermann

2017

Sig Transduct Target Ther

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127

113

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The heterotrimeric Sec61 complex and the dimeric Sec62/Sec63 complex are located in the membrane of the human endoplasmic reticulum (ER) and play a central role in translocation of nascent and newly synthesized precursor polypeptides into the ER. This process involves targeting of the precursors to the membrane and opening of the polypeptide conducting Sec61 channel for translocation. Apart from this central role in the intracellular transport of polypeptides, several studies of the last decade uncovered additional functions of Sec proteins in intracellular signaling: Sec62 can induce ER-phagy in the process of recovery of cells from ER stress and the Sec61 channel can also act as a passive ER calcium leak channel. Furthermore, mutations, amplifications and an overexpression of the SEC genes were linked to various diseases including kidney and liver diseases, diabetes and human cancer. Studies of the last decade could not only elucidate the functional role of Sec proteins in the pathogenesis of these diseases, but also demonstrate a relevance of Sec62 as a prognostic and predictive biomarker in head and neck cancer, prostate and lung cancer including a basis for new therapeutic strategies. In this article, we review the current understanding of protein transport across the ER membrane as central function of Sec proteins and further focus on recent studies that gave first insights into the functional role and therapeutic relevance of Sec61, Sec62 and Sec63 in human diseases.

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Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 57%

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 89%

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 93%

Section: Mutation and Overexpression Of Sec Genesmentioning

confidence: 99%

See 2 more Smart Citations

Let’s talk about Secs: Sec61, Sec62 and Sec63 in signal transduction, oncology and personalized medicine

Linxweiler

Schick

Zimmermann

2017

Sig Transduct Target Ther

Self Cite

127

113

View full text Add to dashboard Cite

show abstract

“…Furthermore, Sec62 was also significantly elevated in more than 80% of thyroid and cervical cancers. In these types of tumors also, ER stress resistance and metastatic capacity were dependent on Sec62 increased protein levels (Linxweiler et al, 2012 , 2016 ). Importantly, increased Sec62 protein levels are evident in post-surgical patients with HBV-related hepatocellular carcinoma recurrence.…”

Section: Selective Autophagy Components In Cancermentioning

confidence: 99%

Hypoxia and Selective Autophagy in Cancer Development and Therapy

Daskalaki

Gkikas

Tavernarakis

2018

Front. Cell Dev. Biol.

133

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Low oxygen availability, a condition known as hypoxia, is a common feature of various pathologies including stroke, ischemic heart disease, and cancer. Hypoxia adaptation requires coordination of intricate pathways and mechanisms such as hypoxia-inducible factors (HIFs), the unfolded protein response (UPR), mTOR, and autophagy. Recently, great effort has been invested toward elucidating the interplay between hypoxia-induced autophagy and cancer cell metabolism. Although novel types of selective autophagy have been identified, including mitophagy, pexophagy, lipophagy, ERphagy and nucleophagy among others, their potential interface with hypoxia response mechanisms remains poorly understood. Autophagy activation facilitates the removal of damaged cellular compartments and recycles components, thus promoting cell survival. Importantly, tumor cells rely on autophagy to support self-proliferation and metastasis; characteristics related to poor disease prognosis. Therefore, a deeper understanding of the molecular crosstalk between hypoxia response mechanisms and autophagy could provide important insights with relevance to cancer and hypoxia-related pathologies. Here, we survey recent findings implicating selective autophagy in hypoxic responses, and discuss emerging links between these pathways and cancer pathophysiology.

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