
Patients with pure mucinous breast cancer (PMBC) have superior recurrence-free interval, recurrence-free survival, and overall survival compared to patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC).


coremsg

Researchers compared outcomes for more than 20,000 women diagnosed with one of three types of breast cancer.

Better Survival Seen With Pure Mucinous Breast Cancer

improved-survival-outcomes-for-patients-with-pure-mucinous-breast-cancer-compared-to-invasive-ductal-and-lobular-carcinomas


Improved Survival Outcomes for Patients with Pure Mucinous Breast Cancer Compared to Invasive Ductal and Lobular Carcinomas


title_rewrite


A reversible, tri-complex RAS inhibitor, RMC-7977, demonstrates potent activity against RAS-addicted tumors carrying various RAS genotypes, particularly KRAS codon 12 mutations, and can inhibit the growth of KRAS(G12C) cancer models resistant to existing KRAS(G12C) inhibitors.


RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type&nbsp;KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated&nbsp;in preclinical models.

Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy - Nature

broad-spectrum-ras-inhibitor-demonstrates-potent-activity-against-various-ras-driven-cancers


Broad-Spectrum RAS Inhibitor Demonstrates Potent Activity Against Various RAS-Driven Cancers



STAT3 acts as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition in KRAS mutant pancreatic cancer.


Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established. Here we identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition. Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. Functional classification of STAT3 responsive program reveals its major role in tumor maintenance and epithelial homeostasis. The signatures of STAT3-activated cell states can be projected onto human KRAS mutant tumors, suggesting that they faithfully reflect characteristics of human disease. These observations have implications for therapeutic intervention and tumor aggressiveness.

Significance The identification of the molecular and genetic characteristics of tumors is essential for understanding disease progression and aggressiveness. KRAS mutations are the most frequent oncogenic drivers in human cancer. In this study we demonstrate that the ubiquitously expressed transcription factor STAT3 is a genetic modifier of TGF-beta-induced EMT, and thereby oncogenic KRAS dependency. Both in vitro and in vivo studies demonstrate that STAT3 responsive program is an inherent part of oncogenic KRAS outcome.

### Competing Interest Statement

The authors have declared no competing interest.

STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer

stat3-as-a-genetic-modifier-of-emt-in-kras-mutant-pancreatic-cancer


STAT3 as a Genetic Modifier of EMT in KRAS Mutant Pancreatic Cancer



FTO plays a crucial role in breast cancer cell proliferation and migration through the regulation of C/EBPβ-LIP expression.


N6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO-knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are being regulated through yet unidentified mechanisms. Differential translation of the CEBPB mRNA into the C/EBPβ transcription factor isoform C/EBPβ-LIP is known to act pro-oncogenic in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBPβ-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBPβ-LIP.

### Competing Interest Statement

The authors have declared no competing interest.

Oncogenic functions of the m6A demethylase FTO in breast cancer cells involving translational upregulation of C/EBPβ-LIP

oncogenic-functions-of-fto-in-breast-cancer-cells


Oncogenic Functions of FTO in Breast Cancer Cells



The author argues that YAP/TAZ enhance P-body formation to promote tumorigenesis by modulating the transcription of P-body-related genes and suppressing the tumor suppressor gene PNRC1.


The role of Processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P- body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P- body formation in CRC cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed codependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1 and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

### Competing Interest Statement

The authors have declared no competing interest.

YAP/TAZ enhance P-body formation to promote tumorigenesis

YAP-TAZ-Role-in-P-Body-Formation-for-Tumorigenesis


YAP/TAZ Role in P-Body Formation for Tumorigenesis



Exclusive expression of miR-200c impedes metastasis formation in vivo and migration in vitro, highlighting its role as a metastatic suppressor in breast cancer.


Advanced breast cancer as well as insufficient treatment can lead to the dissemination of malignant cells from the primary tumor to distant organs. Recent research has shown that miR-200c can hamper certain steps of the invasion-metastasis cascade. However, it is still unclear, whether sole miR-200c expression is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR-200c expression in MDA-MB 231 cells. The ex vivo analysis of metastatic sites in a multitude of organs including lung, liver, brain, and spleen has revealed a dramatically reduced metastatic burden of mice with miR-200c expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR-200c on collective and single cell migration in vitro , utilizing MDA-MB 231 and MCF7 cell systems with genetically modified miR-200c expression. Analysis of collective cell migration has resulted in confluence dependent motility of cells with altered miR-200c expression. Additionally, scratch assays have shown enhanced predisposition of miR-200c negative cells to leave cell clusters. The in-between stage of collective and single cell migration was validated using transwell assays, which have displayed reduced migration of miR-200c positive cells. Finally, to measure migration on single cell level, a novel assay on dumbbell shaped micropatterns was performed, which revealed that miR-200c critically determines confined cell motility. All of these results demonstrate that exclusive expression of miR-200c impedes metastasis formation in vivo and migration in vitro and highlight miR-200c as metastatic suppressor in breast cancer.

### Competing Interest Statement

The authors declare no conflict of interest except for Philipp Paulitschke who is the founder and CEO of PHIO scientific GmbH. He had no role in the design of the study; in the collection and analyses of data; in the writing of the manuscript; or in the decision to publish the results.

Unravelling the metastasis-preventing effect of miR-200c in vitro and in vivo

Unravelling-the-Impact-of-miR-200c-on-Metastasis-in-Breast-Cancer


Unravelling the Impact of miR-200c on Metastasis in Breast Cancer
