Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene<i>FNDC3B</i>

Cai, Chunlin; Rajaram, Megha; Zhou, Xin; Liu, Qing; Marchica, John; Li, Jinyu; Powers, Scott

doi:10.4161/cc.20121

Cited by 70 publications

(74 citation statements)

References 39 publications

(42 reference statements)

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“…FNDC3B is mammary stem cell and cancer cell marker reported by many investigators. [23][24][25][26][27][28] Our earlier report of increased expression of FNDC3B in buffalo mammary cancer 24 was consistent with the present finding of goat mammary cancer. Cyclin B1 (CCNB1) is a cell cycle protein in G2/M transition.…”

supporting

confidence: 81%

Mucin 1 Aberrantly Expresses in Goat Mammary Carcinoma

Choudhary

Verma

et al. 2017

JSRT

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Abbreviations: MUC1, mucin1; qPCR, quantitative polymerase chain reaction; ECM, extra-cellular matrix; PSR, picrosirium red; RT-PCR, reverse transcriptase polymerase chain reaction; MEC, mammary epithelial cells; H&E, hematoxylin and eosin; Ki67, marker of proliferation ki-67; FNDC3B, fibronectin type iii domain containing 3b; CCNB, ccyclin B1; MSI1, musashi 1; PCNA, proliferating cell nuclear antigen IntroductionIncidence of mammary cancer in ruminant is rare. The exact reasons of low incidence of mammary cancer in ruminant are not known. The reason of low incidence of mammary cancer in ruminant is likely due to high rate of pregnancies.1 Hormones like estrogen, play an important role in hyperplasia and neoplasia of mammary tissues and increased parity shortens exposure of estrogen and thus reduce incidence of cancer in goats. In addition to this, other factors such as vegetarian diet with high fiber content, short lifespan of animals, continuous milking of the glands and other factors like mammary stem cells. A survey of screening cancers in goats conducted in Africa and none of the cancer were identified to be the mammary cancer. 2A number of studies proposed stem cells to be the origin of breast cancer 3-5 and these stem cells are dynamic rather than static where progesterone hormone targets mammary stem cells in transforming breast cancer.6 This could be the reason that cancer stem cells share gene signatures with mammary stem cells.7 Incidence of mammary tumors in dogs and cats is very high. In fact, 50% of tumors in dogs are mammary tumors almost three times higher than in woman. The reasons of high incidence of mammary cancer in dogs, cats and human could be dietary habits (meat eater) and high intake of carcinogens through diet as they are higher on food chain.1 Therefore, it deserves attention towards medical perspective as how mammary glands of ruminants (goat) are protected from being cancerous.Mucin 1 (MUC1) encodes for a membrane-bound protein that has essential role in providing protective mucosal barrier and cell signaling. O-glycosylated mucin protein has two terminals, N-terminal alpha subunit (MUC1-N) and C-terminal beta subunit (MUC1-C), former being involved in cell adhesion and later one involved in cell signaling. MUC1 protein is expressed by luminal epithelial cells of mammary tissue on their apical surfaces and provides protective barriers against pathogens. MUC1-N terminal and MUC1-C terminal forms heterodimer and expresses on apical border of mammary epithelial cells. Due to loss of cell polarity, during transformation of normal cell to cancer cell, MUC1-C monomer is positioned entire over the cell membrane. Thus, overexpression and aberrant localization of MUC1-C has been associated with mammary cancer. In general, more than 90% of the mammary cancers overexpress MUC1 proteins. 8However, heterogeneity of MUC1 expression has been seen in 14 breast carcinoma cell lines.9 Variability in amount of MUC1 in breast cancer ranges from high to low expression. High cytoplasmic expression and ab...

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supporting

confidence: 81%

Mucin 1 Aberrantly Expresses in Goat Mammary Carcinoma

Choudhary

Verma

et al. 2017

JSRT

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“…Cai et al . found that FNDC3B overexpression induces the epithelial-to-mesenchymal transition and activates several cancer pathways [33]. In addition, direct evidence from our knockdown and overexpression experiments indicates that FNDC3B promotes cell migration and tumor metastasis in HCC.…”

Section: Discussionmentioning

confidence: 71%

“…However, other evidence highlights FNDC3B as oncogene. First, FNDC3B is usually amplified [7, 33] and highly expressed in HCC and other cancers [7, 31, 34–36]. Cai et al .…”

Section: Discussionmentioning

confidence: 99%

FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma

Lin¹,

Lin²,

Chen³

et al. 2016

Oncotarget

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Recurrence and metastasis are common in hepatocellular carcinoma (HCC) and correlate with poor prognosis. We investigated the role of fibronectin type III domain containing 3B (FNDC3B) in HCC metastasis. Overexpression of FNDC3B in HCC cell lines enhanced cell migration and invasion. On the other hand, knockdown of FNDC3B using short-hairpin RNA reduced tumor nodule formation in both intra- and extra-hepatic metastasis. High levels of FNDC3B were observed in metastatic HCCs and correlated with poor patient survival and shorter recurrence time. Mutagenesis and LC-MS/MS analyses showed that FNDC3B promotes cell migration by cooperating with annexin A2 (ANXA2). Furthermore, FNDC3B and ANXA2 expression correlated negatively with patient survival. Our results indicate that FNDC3B behaves like an oncogene by promoting cell migration. This suggests FNDC3B could serve as a biomarker and therapeutic target for HCC metastasis.

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“…The function of FNDC3B in blood malignancies is unclear, although down-regulation of its expression is known to up-regulate miR-143 expression, which differentiates prostate cancer stem cells and promotes prostate cancer metastasis. 40,41 T-cell reactivity against mut-FNDC3B in patient 2 was polyfunctional (secreting IFN-g, granulocyte macrophage-colony-stimulating factor [GM-CSF], and IL-2), highly avid, and specific to the mut-FNDC3B peptide but not its wild-type counterpart ( Figure 5D). T-cell reactivity was abrogated by the presence of class I blocking antibody (W6/32), indicating that T-cell reactivity was class I restricted ( Figure 5E, left).…”

Section: 40mentioning

confidence: 99%

Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia

Rajasagi

Shukla

Fritsch

et al. 2014

Blood

284

237

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• Tumor neoantigens are a promising class of immunogens based on exquisite tumor specificity and the lack of central tolerance against them.• Massively parallel DNA sequencing with class I prediction enables systematic identification of tumor neoepitopes (including from CLL).Genome sequencing has revealed a large number of shared and personal somatic mutations across human cancers. In principle, any genetic alteration affecting a protein-coding region has the potential to generate mutated peptides that are presented by surface HLA class I proteins that might be recognized by cytotoxic T cells. To test this possibility, we implemented a streamlined approach for the prediction and validation of such neoantigens derived from individual tumors and presented by patient-specific HLA alleles. We applied our computational pipeline to 91 chronic lymphocytic leukemias (CLLs) that underwent whole-exome sequencing (WES). We predicted ∼22 mutated HLA-binding peptides per leukemia (derived from ∼16 missense mutations) and experimentally confirmed HLA binding for ∼55% of such peptides. Two CLL patients that achieved long-term remission following allogeneic hematopoietic stem cell transplantation were monitored for CD8 1 T-cell responses against predicted or confirmed HLA-binding peptides. Long-lived cytotoxic T-cell responses were detected against peptides generated from personal tumor mutations in ALMS1, C6ORF89, and FNDC3B presented on tumor cells. Finally, we applied our computational pipeline to WES data (N 5 2488 samples) across 13 different cancer types and estimated dozens to thousands of predicted neoantigens per individual tumor, suggesting that neoantigens are frequent in most tumors. (Blood. 2014;124(3):453-462) IntroductionRecent progress in the development of potent vaccine adjuvants, clinically effective vaccine delivery systems, and agents that overcome tumor-induced immunosuppression strongly support the possibility that long-awaited effective therapeutic cancer vaccines are feasible. [1][2][3][4] Past cancer vaccine efforts have lacked efficacy that may stem from their focus on overexpressed or selectively expressed tumor-associated native antigens as vaccine targets that require overcoming the challenging hurdles of breaking central and peripheral tolerance while risking the generation of autoimmunity. [4][5][6] The rare examples of successful cancer vaccines in humans have targeted foreign pathogen-associated antigens 7 or a mutated growth factor receptor 8 or are idiotype vaccines derived from patient-specific rearranged immunoglobulins. 9 These studies point to the importance of selecting immunogens distinct from self, where central/peripheral tolerance can be overcome and the risk of autoimmunity is minimal.A hallmark of tumorigenesis is the accumulation of mutations in cancer cells. These mutations are found as both driver and passenger events 10 and collectively provide an opportunity to specifically target tumor cells through the creation of tumor-specific novel immunogenic peptides (neoantigens). ...

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Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogeneFNDC3B

Cited by 70 publications

References 39 publications

Mucin 1 Aberrantly Expresses in Goat Mammary Carcinoma

Mucin 1 Aberrantly Expresses in Goat Mammary Carcinoma

FNDC3B promotes cell migration and tumor metastasis in hepatocellular carcinoma

Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia

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