Promoter hypermethylation inactivate tumor suppressor <i>FAM134B</i> and is associated with poor prognosis in colorectal cancer

Islam, Farhadul; Gopalan, Vinod; Pillai, Suja; Lu, Cu-Tai; Kasem, Kais

doi:10.1002/gcc.22525

Cited by 23 publications

(22 citation statements)

References 41 publications

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“…25). In colorectal cancer, FAM134B functions as a tumor suppressor gene (26), whereas in isocitrate dehydrogenase-mutant gliomas, FAM134B has been identified as a synthetic lethal target (27). These findings reinforce the context-dependent role for selective autophagy programs in cancer.…”

Section: Bulk Degradation and Selective Autophagy Can Both Affect Thementioning

confidence: 71%

Targeting Autophagy in Cancer: Recent Advances and Future Directions

2019

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Autophagy, a multistep lysosomal degradation pathway that supports nutrient recycling and metabolic adaptation, has been implicated as a process that regulates cancer. Although autophagy induction may limit the development of tumors, evidence in mouse models demonstrates that autophagy inhibition can limit the growth of established tumors and improve response to cancer therapeutics. Certain cancer genotypes may be especially prone to autophagy inhibition. Different strategies for autophagy modulation may be needed depending on the cancer context. Here, we review new advances in the molecular control of autophagy, the role of selective autophagy in cancer, and the role of autophagy within the tumor microenvironment and tumor immunity. We also highlight clinical efforts to repurpose lysosomal inhibitors, such as hydroxychloroquine, as anticancer agents that block autophagy, as well as the development of more potent and specifi c autophagy inhibitors for cancer treatment, and review future directions for autophagy research. Signifi cance: Autophagy plays a complex role in cancer, but autophagy inhibition may be an effective therapeutic strategy in advanced cancer. A deeper understanding of autophagy within the tumor microenvironment has enabled the development of novel inhibitors and clinical trial strategies. Challenges and opportunities remain to identify patients most likely to benefi t from this approach.

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Section: Bulk Degradation and Selective Autophagy Can Both Affect Thementioning

confidence: 71%

Targeting Autophagy in Cancer: Recent Advances and Future Directions

2019

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“…Inhibition of RETREG1 contributes to impaired proteostasis in the ER due to the accumulation of misfolded or aggregated proteins, leading to compromised neuronal survival and progressive neuronal degenerative diseases (26). In previous studies, RETREG1 was downregulated in colorectal cancer, and its low expression was associated with younger age, larger tumour size, advanced cancer stages, higher recurrence rate, lymphovascular invasion and poor prognosis of patients (27,28). Furthermore, overexpression of RETREG1 inhibited the proliferation of colorectal cancer cells in vitro, and tumour growth in vivo (29).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑186 promotes cell proliferation and inhibits cell apoptosis in cutaneous squamous cell carcinoma by targeting RETREG1

Liu

et al. 2019

Exp Ther Med

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MicroRNAs (miRs), a class of small non-coding RNAs, have been demonstrated to be involved in the development and progression of human malignancies, including cutaneous squamous cell carcinoma (CSCC). miR-186 serves a suppressive role in certain common types of human cancer; however, its exact function in CSCC has not been reported previously. In the present study, the expression of miR-186 was significantly increased in CSCC tissues compared with adjacent non-tumour tissues. Overexpression of miR-186 significantly promoted CSCC cell proliferation while inhibiting cell apoptosis. Reticulophagy regulator 1 (RETREG1), a gene that is significantly downregulated in CSCC tissues and cell lines, was identified as a novel target of miR-186. In addition, the expression of RETREG1 was inversely correlated with miR-186 expression in CSCC tissues. Furthermore, the expression of RETREG1 was negatively regulated by miR-186 in CSCC cells, and restoration of RETREG1 attenuated the effects of miR-186 on CSCC cells. Taken together, the results of the current study suggest that miR-186 serves an oncogenic role in CSCC and may be used as a potential therapeutic target for the treatment of this disease.

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“…Specifically, it was found that decreased FAM134B expression in colorectal adenocarcinomas is coupled with enhanced tumor aggressiveness, poor prognosis, and tumor re-occurrence as well as metastasis. Deeper analysis showed that in this type of cancer cells, FAM134B was inactivated through promoter methylation and interestingly this effect was found to be tumor stage—specific, i.e., late-stage cancer cells exhibited increased FAM134B promoter methylation in comparison to earlier ones (Islam et al, 2017 , 2018 ). Moreover, in colon cancer cells, an alternative FAM134B inhibition pathway through miR-186-5p, has been revealed rendering FAM134B a tumor suppressor, at least for this type of tumor (Kasem et al, 2014 ; Islam et al, 2017 ).…”

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.

141

103

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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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Promoter hypermethylation inactivate tumor suppressor FAM134B and is associated with poor prognosis in colorectal cancer

Cited by 23 publications

References 41 publications

Targeting Autophagy in Cancer: Recent Advances and Future Directions

Targeting Autophagy in Cancer: Recent Advances and Future Directions

MicroRNA‑186 promotes cell proliferation and inhibits cell apoptosis in cutaneous squamous cell carcinoma by targeting RETREG1

Hypoxia and Selective Autophagy in Cancer Development and Therapy

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