Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP). At some tissues, RBP is recognized by STRA6, a plasma membrane protein that serves a dual role: it transports retinol from extracellular RBP into cells and it transduces a signaling cascade mediated by the Janus kinase JAK2 and the transcription factors STAT3 and STAT5. We show here that expression of RBP and STRA6 is markedly upregulated in human breast and colon tumors, that holo-RBP/STRA6 signaling promotes oncogenic properties, and that STRA6 expression is critical for tumor formation by colon carcinoma cells in vivo. The holo-RBP/STRA6 pathway also efficiently induces fibroblasts to undergo oncogenic transformation, rendering them highly tumorigenic. These data establish that holo-RBP and its receptor STRA6 are potent oncogenes and suggest that the pathway is a novel target for therapy of some human cancers. Cancer Res; 74(21); 1–11. ©2014 AACR.

Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP). At some tissues, RBP is recognized by STRA6, a plasma membrane protein that serves a dual role: it transports retinol from extracellular RBP into cells and it transduces a signaling cascade mediated by the Janus kinase JAK2 and the transcription factors STAT3 and STAT5. We show here that expression of RBP and STRA6 is markedly upregulated in human breast and colon tumors, that holo-RBP/STRA6 signaling promotes oncogenic properties, and that STRA6 expression is critical for tumor formation by colon carcinoma cells in vivo. The holo-RBP/STRA6 pathway also efficiently induces fibroblasts to undergo oncogenic transformation rendering them highly tumorigenic. The data establish that holo-RBP and its receptor STRA6 are potent oncogenes and suggest that the pathway is a novel target for therapy of some human cancers.

The kinase Fer and its spermatogenic meiotic variant, FerT, are coexpressed in normal testes and cancerous tumors, but whether they exert related roles in spermatogenic or malignant cells has not been known. Here, we show that Fer and FerT reside in the mitochondria of spermatogenic cells and are harnessed to the reprogrammed mitochondria of colon carcinoma cells. Both kinases bound complex I of the mitochondrial electron transport chain (ETC) in spermatogenic and in colon carcinoma cells, and silencing of either Fer or FerT was sufficient to impair the activity of this complex. Directed mitochondrial accumulation of FerT in nonmalignant NIH3T3 cells increased their ETC complex I activity, ATP production, and survival, contingent upon stress conditions caused by nutrient and oxygen deprivation. Strikingly, directed mitochondrial accumulation of FerT endowed nonmalignant cells with tumor-forming ability. Thus, recruitment of a meiotic mitochondrial component to cancer cell mitochondria highlights a pivotal role for reprogrammed mitochondria in tumorigenesis. Cancer Res; 74(22); 1–12. ©2014 AACR.

The kinase Fer and its spermatogenic meiotic variant, FerT, are co-expressed in normal testes and cancerous tumors, but whether they exert related roles in spermatogenic or malignant cells has not been known. Here we show that Fer and FerT reside in the mitochondria of spermatogenic cells and are harnessed to the reprogrammed mitochondria of colon carcinoma (CC) cells. Both kinases bound complex I of the mitochondrial electron transport chain (ETC) in spermatogenic and in CC cells and silencing of either Fer or FerT was sufficient to impair the activity of this complex. Directed mitochondrial accumulation of FerT in non-malignant NIH3T3 cells increased their ETC complex I activity, ATP production and survival, contingent upon stress conditions caused by nutrient and oxygen deprivation. Strikingly, directed mitochondrial accumulation of FerT endowed non-malignant cells with tumor-forming ability. Thus, recruitment of a meiotic mitochondrial component to cancer cell mitochondria highlights a pivotal role for reprogrammed mitochondria in tumorigenesis.

Penn’s Abramson Cancer Center and Free to Breathe Philadelphia are teaming up to provide a free day-long lung cancer education conference highlighting prevention, diagnosis, treatment, genetics and life after lung cancer treatment.

Attendees will receive up-to-date information on the latest laboratory research, treatment advances, clinical trials, and survivorship issues.

There are two different sessions for the day, including Focus On Lung Cancer Conference and CANPrevent Lung Cancer Conference. Each session can help those at risk, newly diagnosed or who have survived lung cancer for a long time, find support, answers and possible alternatives to current treatment.

7th Focus On Lung Cancer Conference

Date: Friday, October 17, 2014
Time:  7:30 am to 2:00 pm
Location: Hilton Hotel, 4200 City Avenue, Philadelphia, PA
Looking for information from medical professionals? Learn from expert panels about lung cancer prevention, risk, and quitting smoking.

RSVP for the Focus on Lung Cancer Conference here.

3rd CANPrevent Lung Cancer Conference

Date: Friday, October 17, 2014
Time: 12:30 pm to 2:00 pm
Location: Hilton Hotel, 4200 City Avenue, Philadelphia PA
Are you or a loved one newly touched by lung cancer? Join us for risk assessment, new diagnostics and procedures, surgical advances, information on proton therapy and more.

RSVP the for CANPrevent Lung Cancer Conference here.

Can’t Make the Conference? 

If you can’t make this year’s conference, you can watch or follow the conference live:

• View the Focus On conference live stream online (not active until the day of the events)
• Join @PennCancer on Twitter with the hashtag #LungCancerACC to follow the day’s topics and discussions.
• Join the 9th Annual Free to Breath Run/Walk November 2, 2014