Cet article passe en revue les travaux récents ayant identifié des anomalies moléculaires dans les cellules cancéreuses et le micro-environnement tumoral chez des patients atteints d'un cancer colorectal métastatique

Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer

Li, Weilin ; Ng, Jennifer Mun-Kar ; Wong, Chi Chun ; Ng, Enders Kwok Wai ; Yu, Jun

The term metastasis is widely used to describe the endpoint of the process by which tumour cells spread from the primary location to an anatomically distant site. Achieving successful dissemination is dependent not only on the molecular alterations of the cancer cells themselves, but also on the microenvironment through which they encounter. Here, we reviewed the molecular alterations of metastatic gastric cancer (GC) as it reflects a large proportion of GC patients currently seen in clinic. We [...]

Menée à l'aide de modèles murins et d'échantillons de tissu tumoral et de tissu sain prélevés sur des patients atteints d'un carcinome hépatocellulaire, cette étude met en évidence des mécanismes par lesquels une protéine tyrosine phosphatase, SHP-1, exerce une fonction de suppresseur de tumeurs

SHP-1 acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression

Wen, Liang-Zhi ; Ding, Kai ; Wang, Ze-Rui ; Ding, Chen-hong ; Lei, Shu-juan ; Liu, Jin-pei ; Yin, Chuan ; Hu, Ping-Fang ; Ding, Jin ; Chen, Wan-Sheng ; Zhang, Xin ; Xie, Wei-Fen

Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1, also known as PTPN6), is a nonreceptor protein tyrosine phosphatase that acts as a negative regulator of inflammation. Emerging evidence indicates that SHP-1 plays a role in inhibiting the progression of hepatocellular carcinoma (HCC). However, the role of SHP-1 in hepatocarcinogenesis remains unknown. Here we find that levels of SHP-1 are significantly downregulated in human HCC tissues compared with those in noncancerous [...]

Menée in vitro, cette étude met en évidence des mécanismes par lesquels divers gènes impliqués dans le raccourcissement de la longueur des régions 3'UTR de l'ARN messager, notamment EPS15 et NFIA, répriment la fonction de suppresseur de tumeurs exercée par d'autres gènes, notamment PHF6 et LARP1

3′ UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk

Park, Hyun Jung ; Ji, Ping ; Kim, Soyeon ; Xia, Zheng ; Rodriguez, Benjamin ; Li, Lei ; Su, Jianzhong ; Chen, Kaifu ; Masamha, Chioniso P. ; Baillat, David ; Fontes-Garfias, Camila R. ; Shyu, Ann-Bin ; Neilson, Joel R. ; Wagner, Eric J. ; Li, Wei

Widespread mRNA 3′ UTR shortening through alternative polyadenylation promotes tumor growth in vivo . A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3′UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3′ UTR shortening (MAT3UTR) reveals a significant role in [...]

Menée in vitro et in vivo sur divers modèles de cancer, cette étude met en évidence des mécanismes par lesquels la kinase CDK8 favorise une transition épithélio-mésenchymateuse et le processus invasif

Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer

Serrao, Anne ; Jenkins, Laura M. ; Chumanevich, Alexander A. ; Horst, Ben ; Liang, Jiaxin ; Gatza, Michael L. ; Lee, Nam Y. ; Roninson, Igor B. ; Broude, Eugenia V. ; Mythreye, Karthikeyan

CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase [...]

Cet article passe en revue les travaux récents sur les mécanismes par lesquels les péricytes contribuent à la formation de niches prémétastatiques dans le poumon

Pericytes in the Premetastatic Niche

Paiva, Ana E. ; Lousado, Luiza ; Guerra, Daniel A. P. ; Azevedo, Patrick O. ; Sena, Isadora F. G. ; Andreotti, Julia P. ; Santos, Gabryella S. P. ; Gonçalves, Ricardo ; Mintz, Akiva ; Birbrair, Alexander

The premetastatic niche formed by primary tumor–derived molecules contributes to fixation of cancer metastasis. The design of efficient therapies is limited by the current lack of knowledge about the details of cellular and molecular mechanisms involved in the premetastatic niche formation. Recently, the role of pericytes in the premetastatic niche formation and lung metastatic tropism was explored by using state-of-the-art techniques, including in vivo lineage-tracing and mice with [...]

Menée in vitro et in vivo sur des modèles de cancer de la prostate, cette étude met en évidence des mécanismes par lesquels, via notamment la phosphorylation de la protéine du rétinoblastome, des cellules cancéreuses disséminées entrent dans une phase de dormance au sein d'un tissu osseux

Osteoblast-Secreted Factors Mediate Dormancy of Metastatic Prostate Cancer in the Bone via Activation of the TGFβRIII–p38MAPK–pS249/T252RB Pathway

Yu-Lee, Li-Yuan ; Yu, Guoyu ; Lee, Yu-Chen ; Lin, Song-Chang ; Pan, Jing ; Pan, Tianhong ; Yu, Kai-Jie ; Liu, Bin ; Creighton, Chad J. ; Rodriguez-Canales, Jaime ; Villalobos, Pamela A. ; Wistuba, Ignacio I. ; de Nadal, Eulalia ; Posas, Francesc ; Gallick, Gary E. ; Lin, Sue-Hwa

Bone metastasis from prostate cancer can occur years after prostatectomy, due to reactivation of dormant disseminated tumor cells (DTC) in the bone, yet the mechanism by which DTCs are initially induced into a dormant state in the bone remains to be elucidated. We show here that the bone microenvironment confers dormancy to C4-2B4 prostate cancer cells, as they become dormant when injected into mouse femurs but not under the skin. Live-cell imaging of dormant cells at the single-cell level [...]

Menée à l'aide de modèles murins, cette étude met notamment en évidence des mécanismes par lesquels la protéine kinase PIM-2 réprime l'activité des lymphocytes T CD8+, ce qui suggère l'intérêt de développer des thérapies ciblées sur cette kinase pour augmenter l'efficacité des immunothérapies anticancéreuses

PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity

Daenthanasanmak, Anusara ; Wu, Yongxia ; Iamsawat, Supinya ; Nguyen, Hung D. ; Bastian, David ; Zhang, MengMeng ; Sofi, M. Hanief ; Chatterjee, Shilpak ; Hill, Elizabeth G. ; Mehrotra, Shikhar ; Kraft, Andrew S. ; Yu, Xue-Zhong

PIM kinase family members play a crucial role in promoting cell survival and proliferation via phosphorylation of their target substrates. In this study, we investigated the role of the PIM kinases with respect to T cell responses in transplantation and tumor immunity. We found that the PIM-2 isoform negatively regulated T cell responses to alloantigen, in contrast to the PIM-1 and PIM-3 isoforms, which acted as positive regulators. T cells deficient in PIM-2 demonstrated increased T cell [...]

Cet article passe en revue les travaux récents sur les mécanismes par lesquels, en réponse à des modifications induites par un stress chronique ou aigu, les protéines chaperons sont susceptibles d'intervenir dans la tumorigenèse

Adapting to stress — chaperome networks in cancer

Joshi, Suhasini ; Wang, Tai ; Araujo, Thaís L. S. ; Sharma, Sahil ; Brodsky, Jeffrey L. ; Chiosis, Gabriela

In this Opinion article, we aim to address how cells adapt to stress and the repercussions chronic stress has on cellular function. We consider acute and chronic stress-induced changes at the cellular level, with a focus on a regulator of cellular stress, the chaperome, which is a protein assembly that encompasses molecular chaperones, co-chaperones and other co-factors. We discuss how the chaperome takes on distinct functions under conditions of stress that are executed in ways that differ [...]