Hypoxia promotes EV secretion by impairing lysosomal homeostasis in HNSCC through negative regulation of ATP6V1A by HIF-1α.

Tumour cells under hypoxia tend to modulate the number and contents of extracellular vesicles (EVs) to regulate the tumour microenvironment (TME) and thus promote tumour progression. However, the mechanism of how hypoxia influences the secretion of EVs remains to be elucidated. Here, we confirm the increased production of EVs in head and neck squamous cell carcinoma (HNSCC) cells under hypoxia, where endosome-derived EVs are the main subtype affected by insufficient O2 . The accumulation of hypoxia-inducible factor-1α (HIF-1α) under hypoxia directly downregulates the expression of ATP6V1A, which is pivotal to maintain the homeostasis of lysosomes. Subsequently, impaired lysosomal degradation contributes to the reduced fusion of multivesicular bodies (MVBs) with lysosomes and enables the secretion of intraluminal vesicles (ILVs) as EVs. These findings establish a HIF-1α-regulated lysosomal dysfunction-EV release axis and provide an exquisite framework to better understand EV biogenesis.

Chronic progression of recurrent orthokeratinized odontogenic cyst into squamous cell carcinoma: A case report.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC) is a benign odontogenic cyst. It is a variant of the common odontogenic keratocyst (OKC). This case report describes a rare malignant transformation of OOC, with the aim of raising awareness of the malignant potential of OOC and distinguishing it from OKC. CASE SUMMARY: In August 2018, a 52-year-old man was referred to the Department of Oral Maxillofacial and Head-Neck Oncology of Wuhan University. The patient presented with severe pain in the left mandible for 2 mo, and had a 5-year history of osteomyelitis and mandibular cyst with three recurrences. His latest diagnosis by pathological examination was OOC of the left mandible with mild-to-moderate local proliferation. However, the cyst showed malignant potential by radiographic examination. We performed partial mandibulectomy and sent the lesion tissue for pathological examination. As expected, the cyst had deteriorated to moderately differentiated squamous cell carcinoma. During postoperative follow-up, the patient went for chemotherapy in September 2018 and successfully completed four cycles. CONCLUSION: Surgeons should be more aware of OOC, which is usually benign but can become malignant.