Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast

An, Yeji; Adams, Jessica R.; Hollern, Daniel P.; Zhao, Anthony; Chang, Stephen G.; Gams, Miki S.; Chung, Philip E.D.; He, Xiaping; Jangra, Rhea; Shah, Juhi S.; Yang, Joanna; Beck, Lauren A.; Raghuram, Nandini; Kozma, Katelyn J.; Loch, Amanda J.; Wang, Wei; Fan, Cheng; Done, Susan J.; Zacksenhaus, Eldad; Guidos, Cynthia J.; Perou, Charles M.; Egan, Sean E.

doi:10.1016/j.celrep.2018.09.056

Cited by 51 publications

(51 citation statements)

References 57 publications

(88 reference statements)

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“…Cadherins are important in the maintenance of cell adhesion and polarity, and alterations of these functions can contribute to tumorigenesis. CDH1 germline mutations have been associated with hereditary lobular breast cancer [61] and hereditary diffuse gastric cancer [62,63], while a recent study linked mutations in CDH1 and PIK3CA to the immune-related invasive lobular carcinoma of the breast [64]. In breast cancer, mutations in CDH1-PIK3CA module are mutually exclusive with mutations in TP53 and are strongly enriched in Luminal A subtype [65].…”

Section: Identifying Mutated Subnetwork Associated With Mutational Smentioning

confidence: 99%

Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer

et al. 2020

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Background: Studies of cancer mutations have typically focused on identifying cancer driving mutations that confer growth advantage to cancer cells. However, cancer genomes accumulate a large number of passenger somatic mutations resulting from various endogenous and exogenous causes, including normal DNA damage and repair processes or cancer-related aberrations of DNA maintenance machinery as well as mutations triggered by carcinogenic exposures. Different mutagenic processes often produce characteristic mutational patterns called mutational signatures. Identifying mutagenic processes underlying mutational signatures shaping a cancer genome is an important step towards understanding tumorigenesis. Methods: To investigate the genetic aberrations associated with mutational signatures, we took a network-based approach considering mutational signatures as cancer phenotypes. Specifically, our analysis aims to answer the following two complementary questions: (i) what are functional pathways whose gene expression activities correlate with the strengths of mutational signatures, and (ii) are there pathways whose genetic alterations might have led to specific mutational signatures? To identify mutated pathways, we adopted a recently developed optimization method based on integer linear programming. Results: Analyzing a breast cancer dataset, we identified pathways associated with mutational signatures on both expression and mutation levels. Our analysis captured important differences in the etiology of the APOBEC-related signatures and the two clock-like signatures. In particular, it revealed that clustered and dispersed APOBEC mutations may be caused by different mutagenic processes. In addition, our analysis elucidated differences between two age-related signatures-one of the signatures is correlated with the expression of cell cycle genes while the other has no such correlation but shows patterns consistent with the exposure to environmental/external processes. Conclusions: This work investigated, for the first time, a network-level association of mutational signatures and dysregulated pathways. The identified pathways and subnetworks provide novel insights into mutagenic processes that the cancer genomes might have undergone and important clues for developing personalized drug therapies.

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Section: Identifying Mutated Subnetwork Associated With Mutational Smentioning

confidence: 99%

Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer

et al. 2020

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“…[ 169 ] Recent evidence suggests that PI3K‐Akt signaling also inhibits the Hippo pathway to promote YAP/TAZ activation to drive cell proliferation and malignancy. [ 99,115,170‐178 ] Importantly, further work is necessary to identify the molecular mechanism by which PI3K‐Akt signaling inhibits the Hippo pathway. In addition, while PI3K‐Akt signaling appears necessary to promote YAP/TAZ activation, it is apparently not sufficient, as cells also require mechanical stimulation or other additional inputs to activate YAP/TAZ.…”

Section: Introductionmentioning

confidence: 99%

“…There is some evidence that YAP/TAZ may confer resistance of cancer cells to immunotherapy, through upregulation of PD‐L1 expression, [ 82 ] or through regulation of macrophages/myeloid derived suppressor cell (MDSC) cell infiltrates. [ 86,100,177,178,286 ] Thus, targeting YAP/TAZ may be an ideal “adjuvant” for combination with immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

2020

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The transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1) are frequently activated during the growth and progression of many solid tumors, including lung, colorectal, breast, pancreatic, and liver carcinomas as well as melanoma and glioma. YAP/TAZ bind to TEAD-family co-activators to drive cancer cell survival, proliferation, invasive migration, and metastasis. YAP/TAZ activation may also confer resistance to chemotherapy, radiotherapy, or immunotherapy. YAP-TEAD cooperates with the RAS-induced AP-1 (FOS/JUN) transcription factor to drive tumor growth and cooperates with MRTF-SRF to promote activation of cancer-associated fibroblasts, matrix stiffening, and metastasis. The key upstream repressor of YAP/TAZ activation is the Hippo (MST1/2-LATS1/2) pathway and the key upstream activators are mechanically induced Integrin-SRC and E-cadherin-AJUBA/TRIP6/LIMD1, growth factor induced PI3K-AKT, and inflammation-induced G-protein coupled receptor (GPCR) signals, all of which antagonize the Hippo pathway. In this review, strategies to target YAP/TAZ activity in cancer are discussed along with the prospects for synergy with established pillars of cancer therapy.

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“…With relative high cellular throughput and high dimensions, CyTOF is an ideal and potent technique that reveals intratumor heterogeneity in a variety of tumors, including breast, [70][71][72][73] lung, [74][75][76][77] oropharyngeal, 78 brain, [79][80][81][82][83] colon, 7,11,84,85 ovarian, 86,87 kidney, 88,89 gastric cancer, 90,91 leukemia and lymphoma, 19,[92][93][94][95] and melanoma. 96,97 A summary of single-cell CyTOF studies on primary tumors of various human cancers is presented in Table 3.…”

Section: Cancermentioning

confidence: 99%

Progress and applications of mass cytometry in sketching immune landscapes

Zhang

Warden

2020

Clinical & Translational Med

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Recently emerged mass cytometry (cytometry by time-of-flight [CyTOF]) technology permits the identification and quantification of inherently diverse cellular systems, and the simultaneous measurement of functional attributes at the single-cell resolution. By virtue of its multiplex ability with limited need for compensation, CyTOF has led a critical role in immunological research fields. Here, we present an overview of CyTOF, including the introduction of CyTOF principle and advantages that make it a standalone tool in deciphering immune mysteries. We then discuss the functional assays, introduce the bioinformatics to interpret the data yield via CyTOF, and depict the emerging clinical and research applications of CyTOF technology in sketching immune landscape in a wide variety of diseases.

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Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast

Cited by 51 publications

References 57 publications

Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer

Network-based approaches elucidate differences within APOBEC and clock-like signatures in breast cancer

YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

Progress and applications of mass cytometry in sketching immune landscapes

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