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Abstract Background Caveolae proteins play diverse roles in cancer development and progression. In prostate cancer, non‐caveolar caveolin‐1 (CAV1) promotes metastasis, while CAVIN1 attenuates CAV1‐induced metastasis. Here, we unveil a novel mechanism linking CAV1 to selective loading of exosomes with metastasis‐promoting microRNAs. Results We identify hnRNPK as a CAV1‐regulated microRNA binding protein. In the absence of CAVIN1, non‐caveolar CAV1 drives localisation of hnRPNK to multi‐vesicular bodies (MVBs), recruiting AsUGnA motif‐containing miRNAs and causing their release within exosomes. This process is dependent on the lipid environment of membranes as shown by cholesterol depletion using methyl‐β‐cyclodextrin or by treatment with n‐3 polyunsaturated fatty acids. Consistent with a role in bone metastasis, knockdown of hnRNPK in prostate cancer PC3 cells abolished the ability of PC3 extracellular vesicles (EV) to induce osteoclastogenesis, and biofluid EV hnRNPK is elevated in metastatic prostate and colorectal cancer. Conclusions Taken together, these results support a novel pan‐cancer mechanism for CAV1‐driven exosomal release of hnRNPK and associated miRNA in metastasis, which is modulated by the membrane lipid environment.

Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here, we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 may be attributed to its negative regulation of uL18, leading to p53 inactivation.

Tumors evolve in complex and dynamic microenvironments that they rely on for sustained growth, invasion, and metastasis. Within this space, tumor cells and non-malignant cells are in frequent communication. One specific mode of communication that has gained recent attention is the release of extracellular vesicles (EVs). EVs are lipid bilayer-bound vehicles that are released from the cell membrane and carry nucleic acids, proteins, and lipids to neighboring or distant cells. EVs have been demonstrated to influence a multitude of processes that aid in tumor progression including cellular proliferation, angiogenesis, migration, invasion, metastasis, immunoediting, and drug resistance. The ubiquitous involvement of EVs on cancer progression makes them very suitable targets for novel therapeutics. Furthermore, they are being studied as specific markers for cancer diagnostics, prognosis, and even as chemotherapy drug-delivery systems. This review focuses on the most recent advances in EV knowledge, some current and potential problems with their use, and some proposed solutions to consider for the future.

The timing of elective surgery for the treatment of diverticular disease is constantly evolving. Historically, the indications for elective surgery were relatively consistent. It was recommended that patients undergo elective resection after two documented attacks of uncomplicated diverticulitis or after one attack of complicated diverticulitis in which the patient did not require emergent surgery. There were some exceptions to these guidelines; people <50 years old could undergo elective resection after their first attack, and patients who had previous solid organ transplants could undergo resection after a single attack. In this article, the author updates the data regarding the timing of surgery in elective diverticular disease and challenges surgical dogma. [ABSTRACT FROM AUTHOR]